Percentage Of Peripheral Blood CD4 Research Articles

Identification and characterization of circulating and adipose tissue infiltrated CD20+T cells from subjects with obesity that undergo bariatric surgery

T cells play critical roles in adipose tissue (AT) inflammation. The role of CD20+T cell in AT dysfunction and their contributing to insulin resistance (IR) and type 2 diabetes progression, is not known. The aim was to characterize CD20+T cells in omental (OAT), subcutaneous (SAT) and peripheral blood (PB) from subjects with obesity (OB, n = 42), by flow cytometry. Eight subjects were evaluated before (T1) and 12 months post (T2) bariatric/metabolic surgery (BMS). PB from subjects without obesity (nOB, n = 12) was also collected. Higher percentage of CD20+T cells was observed in OAT, compared to PB or SAT, in OB-T1. CD20 expression by PB CD4+T cells was inversely correlated with adiposity markers, while follicular-like CD20+T cells were positively correlated with impaired glucose tolerance (increased HbA1c). Notably, among OB-T1, IR establishment was marked by a lower percentage and absolute number of PB CD20+T cells, compared nOB. Obesity was associated with higher percentage of activated CD20+T cells; however, OAT-infiltrated CD20+T cells from OB-T1 with diabetes displayed the lowest activation. CD20+T cells infiltrating OAT from OB-T1 displayed a phenotype towards IFN-γ-producing Th1 and Tc1 cells. After BMS, the percentage of PB CD4+CD20+T cells increased, with reduced Th1 and increased Th17 phenotype. Whereas in OAT the percentage of CD20+T cells with Th1/17 and Tc1/17 phenotypes increased. Interestingly, OAT from OB pre/post BMS maintained higher frequency of effector memory CD20+T cells. In conclusion, CD20+T cells may play a prominent role in obesity-related AT inflammation.

CD4+ T cells and TGFβ1/MAPK signal pathway involved in the valvular hyperblastosis and fibrosis in patients with rheumatic heart disease

The aim of this study was to investigate the roles of CD4+ T cells and transforming growth factor beta (TGFβ1) in the pathological process of valvular hyperblastosis and fibrosis of patients with rheumatic heart disease (RHD). A total of 151 patients were enrolled, among whom, 78 patients were with RHD, and 73 were age and gender matched RHD negative patients. Blood samples and valve specimens were collected for analysis. Pathological changes and collagen fibers contents of valves were analyzed using HE and Masson staining. Percentage of peripheral blood CD4+ T cells was tested through flow cytometry. TGFβ1 level in serum were identified by ELISA. CD4+ T cells infiltration and expression of TGFβ1, p-p38, p-JNK, p-ERK in valves were detected by immunohistochemistry. The mRNA and protein levels of p38, JNK, ERK, TGFβ1, I-collagen and α-SMA were detected by qRT-PCR and western blotting, respectively. The heart valve tissues of RHD patients showed higher degrees of fibrosis, calcification and lymphocytes infiltration, which were mainly CD4+ T cells. In addition, compared with control group, RHD patients had more total CD4+ T cells in peripheral blood and valve tissues. Expression of TGFβ1, phosphorylation of JNK and p38, and synthesis of I-collagen in valve tissues of RHD patients were also significantly increased. Furthermore, we found a strong positive correlation between TGFβ1 expression and phosphorylation of JNK and p38. CD4+ T cells, and fibrogenic cytokine TGFβ1, which activate the intracellular MAPK signaling pathway may participate in the fibrosis of heart valve in RHD patients.

Relationship of T lymphocytes, cytokines, immunoglobulin E and nitric oxide with otitis media with effusion in children and their clinical significances.

To investigate the relations of T lymphocytes, cytokines, immunoglobulin E, and nitric oxide with otitis media with effusion (OME) in children and their clinical significances. Fifty children with OME treated in our hospital were enrolled in the study (observation group). Fifty healthy children were selected as control. The percentages of CD4+ and CD8+ T lymphocyte and CD4+/CD8+ ratio in peripheral blood, and the levels of cytokine (IL)-2, IL-4, IL-6, immunoglobulin E (IgE) and nitric oxide (NO) in peripheral blood and middle ear effusion (MEE) in both groups were detected. The correlations of these indexes with OME were analyzed. The percentage of peripheral blood CD4+ and CD8+ levels, CD4+/CD8 ratio, IgE, and NO levels in the observation group were significantly higher than those in the control group (P < 0.01). In the observation group, the IL-2 and IL-6 levels, and IgE and NO levels in the MEE were significantly higher than those in peripheral blood (P < 0.01). In addition, in the observation group, the MEE IL-2 and IL-6 levels were positively correlated with peripheral blood CD4+/CD8+ ratio, respectively r = 0.366, P = 0.009; r = 0.334, P = 0.018. The levels of peripheral blood CD4+ and CD8+ lymphocytes and MEE IL-2, IL-6, IgE, and NO levels are increased in children with OME. These indexes have provided significant clues for the diagnosis of OME in children.

Percentage and function of CD4+CD25+ regulatory T cells in patients with hyperthyroidism.

The current study observed the percentage of peripheral blood (PB) CD4+CD25+ regulatory T cells (Tregs) and the influence of CD4+CD25+ Tregs on the proliferation of naïve CD4 T cells in patients with hyperthyroidism. Furthermore, preliminary discussions are presented on the action mechanism of CD4+CD25+ Tregs on hyperthyroidism attacks. The present study identified that compared with the percentage of PB CD4+CD25+ Tregs in healthy control subjects, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism (P>0.05). For patients with hyperthyroidism, CD4+CD25+ Tregs exhibited significantly reduced inhibition of the proliferation of naïve CD4 T cells and decreased secretion capacity on the cytokines of CD4 T cells, compared with those of healthy control subjects (P<0.05). In addition, it was demonstrated that thyroid function of patients with hyperthyroidism was significantly improved (P<0.05) subsequent to receiving medication. Compared with the percentage of PB CD4+CD25+ Tregs in patients with hyperthyroidism before treatment, no significant changes were observed in the percentage of PB CD4+CD25+ Tregs in hyperthyroidism patients following treatment (P>0.05). In the patients with hyperthyroidism, following treatment, CD4+CD25+ Tregs exhibited significantly increased inhibition of the proliferation of naïve CD4 T cells and increased secretion capacity of CD4 T cell cytokines, compared with those of the patients with hyperthyroidism prior to treatment (P<0.05). PB CD4+CD25+ Tregs function was decreased in patients with hyperthyroidism, and its non-proportional decrease may be closely associated with the occurrence and progression of hyperthyroidism.

Immunomodulatory effects of herbal formula of astragalus polysaccharide (APS) and polysaccharopeptide (PSP) in mice with lung cancer

ObjectiveThis study is to investigate the immunomodulatory effects of the herbal formula of astragalus polysaccharide (APS) and polysaccharopeptide (PSP) in mouse models of immunosuppression and lung cancer. MethodsImmune parameters were recorded for these model mice. Peripheral white blood cells (WBC) were detected with the automatic blood cell analyzer. Spleen and thymus indices, and tumor inhibition ratio were obtained. Percentage of peripheral blood CD4+ and CD8+ T lymphocytes were detected by flow cytometry. Serum levels of Th1 (IL-2, TNF, and IFN-γ), Th2 (IL-4, IL-6, and IL-10), and Th17 (IL-17A) were detected with the BD cytometric bead array (CBA) mouseTh1/Th2/Th17 cytokine kit. ResultsCompared with the NS group, the PSP and APS herbal formula significantly improved the WBC, thymus index, spleen index, CD4+/CD8+ ratio, TNF, IFN-γ, IL-2, andIL-17Ainimmunosuppressivemice and lung cancer mice (P<0. 05). On the contrary, IL-10 was relatively low in the PSP+APS herbal formula group (P<0. 05). Besides, the PSP+APS herbal formula group induced comparable tumor inhibiting effect with the AMD group (23.3% and 24.1%, respectively). ConclusionThe PSP+APS herbal formula have immunomodulatory effects and anti-tumor activity in mice with of lung cancer.

Significant reduction of peripheral blood interleukin-35 and CD4+EBI3+ T cells, which are negatively correlated with an increase in the plasma IL-17 and cTnI level, in viral myocarditis patients.

IntroductionViral myocarditis (VMC) has become an increasingly common heart disease that endangers human health. In the present study, the plasma interleukin-35 (IL-35) level and the percentage of CD4+EBI3+ T cells in VMC patients were detected to investigate the significance of changes in these parameters in the plasma of VMC patients and their association with the disease.Material and methodsELISA was performed to detect the plasma IL-35 level and the percentage of peripheral blood CD4+EBI3+ T cells in 40 VMC patients and in 20 healthy individuals. Moreover, the plasma IL-17 levels in the VMC patients and in the healthy individuals were detected using an ELISA, and the cardiac Troponin-I (cTnI) levels were detected using a chemiluminescent microparticle immunoassay to compare the differences in the groups.ResultsPlasma IL-35 level and the percentage of CD4+EBI3+ T cells in acute phase VMC patients was lower than that in the healthy control group and the convalescent phase VMC patients. Additionally, the plasma IL-35 level in the VMC patients exhibited a negative correlation with the levels of cTnI and IL-17. The percentage of CD4+EBI3+ T cells also showed a negative correlation with the levels of cTnI and IL-17.ConclusionsThe plasma IL-35 level and the percentage of CD4+EBI3+ T cells in VMC patients was reduced, and the amount of the decrease was associated with the severity of the disease. These results suggest that IL-35 and CD4+EBI3+ T might play important roles in the progression of VMC and could be used as indictors of the disease.

Th17 cells reflect colon submucosal pathologic changes in active eosinophilic granulomatosis with polyangiitis.

BackgroundChronic eosinophilic pneumonia (CEP) or eosinophilic gastroenteritis (EG), or both, with asthma precede the onset of eosinophilic granulomatosis with polyangiitis (EGPA) in half of all EGPA patients. It is not known what determines whether patients with CEP or with EG following asthma will develop EGPA.MethodsWe studied 17 EGPA patients and 12 patients with CEP but without EGPA. We assayed serum ICAM-1, VCAM-1, and VEGF, and the percentage of peripheral blood CD4+ T cells producing IL-17 (Th17 cells), at both onset and remission. We also examined the numbers of submucosal eosinophils and the basement membrane-to-crypt and crypt-to-crypt distance to evaluate edema in the colon submucosa at onset and remission in EGPA and at onset in CEP.ResultsNine of 12 (75.0 %) CEP patients had symptoms or endoscopic findings. Colonic submucosal eosinophil counts and edema in EGPA at onset were greater than at remission or in CEP at onset. Th17 cells (%) and serum ICAM-1 levels at onset were greater in EGPA than in CEP. In EGPA, peripheral blood Th17 cells (%) were significantly correlated with serum ICAM-1 level, colonic submucosal eosinophil count, and degree of edematous change; inversely correlated with serum VEGF level; but not correlated with VCAM-1 level.ConclusionsEosinophilia and colonic submucosal edematous change were greater in EGPA than in CEP. The mechanism of vasculitis in EGPA appears related to increases in serum Th17 cell numbers and ICAM-1 levels and decreases in VEGF levels.

Expression and clinical significance of CD4+ CD45+ peripheral blood T cells in patients with ulcerative colitis.

The objectives of this study were to explore the expression of peripheral blood CD4+CD45+ T cells in patients with ulcerative colitis (UC) and determine its clinical value. We selected 80 patients with UC from the First Affiliated Hospital of Liaoning Medical University from March 2012 to December 2013. Of these, 27 had mildly active, 28 moderately active, and 25 severely active UC. We also recruited 80 subjects to constitute the healthy control group. The percentages of CD4+CD45+ molecules on the peripheral blood T cell surfaces of patients were detected using flow cytometry and were compared between patients to determine the severity of illness. The percentage of peripheral blood CD4+CD45+T cells in the UC group was 52.93 ± 3.64% and in the controls it was 41.34 ± 2.94%; the UC group percentages were significantly higher (t = -22.159, P < 0.05). The average percentages in patients with mild, moderate, and severe activity were 50.99 ± 1.45, 52.66 ± 1.41, and 55.18 ± 2.18%, respectively; the moderate activity percentage was higher than that of mild activity, and the severely active stage percentage was overall the highest. Comparison between groups showed a statistically significant difference, F = 39.850, (P < 0.05). The expression levels of peripheral blood CD4+CD45+ T cells in the UC group were higher than those in the control group. Overall, our results showed that with the aggravation of disease the peripheral blood CD4+CD45+ T cell percentages were significantly increased, which might be useful as a marker for clinical diagnosis.

Anabolic Steroid-Induced Hepatitis and Portal Gastropathy in a Young Bodybuilder

[Introduction] Virtual Touch Tissue Quantification (VTTQ) is an ultrasound technique to quantify tissue stiffness based on measurement of the propagation velocity of elastic shearwaves (Vs) generated by acoustic radiation force impulses that cause tissue displacements. [Objective] To explore the usefulness of liver and spleen stiffness measurements by VTTQ for diagnostic differentiation between idiopathic portal hypertension (IPH) and portal hypertension caused by liver cirrhosis (LC). [Subjects] Thirteen patients with histologically diagnosed IPH and 18 patients with histologically diagnosed LC were recruited for this study. Eight normal subjects (NC) and 7 patients with chronic hepatitis (CH) were also included. [Methods] With the region of interest (ROI) set at a 3-cm depth from the body surface, the mean of 5 successful Vs measurements of the liver and spleen in each patient was determined. The percentage of peripheral blood CD4+ CD25+ T cells (Tregs) in the LC cases and IPH cases was analyzed by FACS, and the size of the spleen (SI) was also measured. [Results] The measured stiffness of the liver (NC: CH: LC: IPH = 1.14: 1.40: 2.50: 1.56 m/s) was greater in the LC patients (p < 0.001), and that of the spleen (2.03: 2.30: 3.12: 3.90) was greater in the patients with IPH (p < 0.001). Making each ROC curve, we set the cut-off values of liver stiffness by VTTQ as follows (CH: LC: IPH = 1.14: 1.54: 1.23 m/s). The sensitivities were (89.5: 94.7: 89.5%) and the specificities were (62.5: 100.0: 75.0%). Meanwhile, setting the cut-off values of spleen stiffness as follows (CH: LC: IPH = 2.44: 2.61: 2.88 m/s), the sensitivities were (66.7: 90.5: 90.5%) and the specificities were (87.5: 100.0: 100.0%). The stiffness measurements of both liver and spleen were proved to be useful in diagnosis. Furthermore, a lower peripheral blood Tregs frequency [(LC: IPH) = (19.0: 11.6%)] (p < 0.001) and a larger SI (22.5: 44.5) (p < 0.001) were recorded in the IPH patients. [Discussion] The IPH patient group showed a lower liver stiffness relative to the LC group and comparable liver stiffness to that in the CH group. Stiffness of the spleen, nevertheless, was markedly higher in the IPH group; thus, stiffness measurements of both the liver and spleen allowed ready diagnostic differentiation between portal hypertension associated with LC and IPH. The increased splenic stiffness with splenomegaly in IPH was considered to be attributable to a state of enhanced immune functions when viewed with reference to the reduced percentage of peripheral blood Tregs.

Elucidation of Idiopathic Portal Hypertension Based on Liver and Spleen Stiffness Measurements by Virtual Touch Tissue Quantification and Peripheral Blood CD4+ CD25+ T Cytometry

[Introduction] Virtual Touch Tissue Quantification (VTTQ) is an ultrasound technique to quantify tissue stiffness based on measurement of the propagation velocity of elastic shearwaves (Vs) generated by acoustic radiation force impulses that cause tissue displacements. [Objective] To explore the usefulness of liver and spleen stiffness measurements by VTTQ for diagnostic differentiation between idiopathic portal hypertension (IPH) and portal hypertension caused by liver cirrhosis (LC). [Subjects] Thirteen patients with histologically diagnosed IPH and 18 patients with histologically diagnosed LC were recruited for this study. Eight normal subjects (NC) and 7 patients with chronic hepatitis (CH) were also included. [Methods] With the region of interest (ROI) set at a 3-cm depth from the body surface, the mean of 5 successful Vs measurements of the liver and spleen in each patient was determined. The percentage of peripheral blood CD4+ CD25+ T cells (Tregs) in the LC cases and IPH cases was analyzed by FACS, and the size of the spleen (SI) was also measured. [Results] The measured stiffness of the liver (NC: CH: LC: IPH = 1.14: 1.40: 2.50: 1.56 m/s) was greater in the LC patients (p < 0.001), and that of the spleen (2.03: 2.30: 3.12: 3.90) was greater in the patients with IPH (p < 0.001). Making each ROC curve, we set the cut-off values of liver stiffness by VTTQ as follows (CH: LC: IPH = 1.14: 1.54: 1.23 m/s). The sensitivities were (89.5: 94.7: 89.5%) and the specificities were (62.5: 100.0: 75.0%). Meanwhile, setting the cut-off values of spleen stiffness as follows (CH: LC: IPH = 2.44: 2.61: 2.88 m/s), the sensitivities were (66.7: 90.5: 90.5%) and the specificities were (87.5: 100.0: 100.0%). The stiffness measurements of both liver and spleen were proved to be useful in diagnosis. Furthermore, a lower peripheral blood Tregs frequency [(LC: IPH) = (19.0: 11.6%)] (p < 0.001) and a larger SI (22.5: 44.5) (p < 0.001) were recorded in the IPH patients. [Discussion] The IPH patient group showed a lower liver stiffness relative to the LC group and comparable liver stiffness to that in the CH group. Stiffness of the spleen, nevertheless, was markedly higher in the IPH group; thus, stiffness measurements of both the liver and spleen allowed ready diagnostic differentiation between portal hypertension associated with LC and IPH. The increased splenic stiffness with splenomegaly in IPH was considered to be attributable to a state of enhanced immune functions when viewed with reference to the reduced percentage of peripheral blood Tregs.

Expression and significance of peripheral blood CD4 + CD28 - T cells in patients with autoimmune hepatitis

The percentage of peripheral blood CD4 + CD28 - T cell in 59 patients with autoimmune hepatitis (AIH) (36 with active disease and 23 stable) and 30 normal individuals was evaluated by twocolor flowcytometry. IL-10 and TNF-α levels were assayed by double-antibody sandwich ELISA. Serum immunoglobulin were also analyzed. Patient with active AIH had significantly higher peripheral blood CD4 + CD28 - T cell and TNF-α levels than normal individuals ( P ＜ 0. 05 ), while in patients with remission they were only slightly higher than normal controls. If remission was induced in patients with active AIH,peripheral blood CD4 + CD28 - T cell percentage would be significantly reduced ( P ＜ 0. 05 ) while IL-10 increased ( P ＜ 0. 05 ). The percentage of peripheral blood CD4 + CD28 - T cell in patients with relapse was significantly higher than newly diagnosed patients and normal controls; Peripheral blood CD4 + CD28 -T cell percentage in patients with abnormal serum immunoglobulin ( IgA, IgG and IgM ) levels was significantly higher than those with normal levels and normal controls. We concluded that abnormal peripheral blood CD4 + CD28- T cells and cytokine in patients with AIH may be related to disease activity and clinical manifestations, which may also play a role in the pathogenesis of AIH. Key words: Hepatitis, autoimmune; T-lymphocytes

Phase I Safety and Pharmacokinetic Study of CT-011, a Humanized Antibody Interacting with PD-1, in Patients with Advanced Hematologic Malignancies

CT-011 is a humanized IgG1 monoclonal antibody that modulates the immune response through interaction with PD-1, a protein belonging to the B7 receptor family present on lymphocytes. The objectives of this phase I study were to assess the dose-limiting toxicities, to determine the maximum tolerated dose, and to study the pharmacokinetics of CT-011 administered once to patients with advanced hematologic malignancies. Seventeen patients were treated with escalating doses of CT-011 ranging from 0.2 to 6 mg/kg. For pharmacokinetic analysis, blood samples were withdrawn from the patients before and immediately after treatment and at 24 hours, 48 hours, and on days 7, 14, and 21. CT-011 blood levels were assessed with a specific ELISA and derived concentrations were used to calculate pharmacokinetic parameters. Activation of the immune system was assessed by measuring peripheral blood CD4+, CD8+, and CD69+ lymphocytes. The study showed the antibody to be safe and well tolerated in this patient population. No single maximum tolerated dose was defined in this study. Clinical benefit was observed in 33% of the patients with one complete remission. Pharmacokinetic analyses show that serum Cmax and the AUC of CT-011 increased proportionally with dose. The median t1/2 of CT-011 ranged from 217 to 410 hours. Sustained elevation in the percentage of peripheral blood CD4+ lymphocytes was observed up to 21 days following CT-011 treatment. A single administration of 0.2 to 6.0 mg/kg of CT-011 is safe and well tolerated in patients with advanced hematologic malignancies.

Effect of house dust mite immunotherapy on transforming growth factor β1-producing T cells in asthmatic children

Recent evidence suggests that regulatory T cells (Treg cells) and immunosuppressive cytokines, such as transforming growth factor BETA1 (TGF-BETA1) and interleukin 10 (IL-10), may have a role in clinically effective allergen specific immunotherapy (SIT). To evaluate the effect of SIT on the induction of Treg cells in house dust mite-allergic children and on the expression of specific Treg cell markers (cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], IL-10, and TGF-BETA1). In this uncontrolled open-label study, the percentage of peripheral blood CD4+ Treg cells (CD69 CD45RO+CTLA-4+ and CD3+CD4+CD25+FOXP3+) and the expression of molecules associated with their functions (CTLA-4, TGF-BETA1, and IL-10) were analyzed using flow cytometry in 16 children allergic to house dust mites before and at 3 and 12 months of subcutaneous SIT. Clinical variables, such as symptom score, medication requirements, forced expiratory volume in 1 second, peak expiratory flow rate, and serum IgE levels, were also determined. Ten healthy children were included as controls. All the clinical variables improved during immunotherapy. The percentage of CD4+CD25+CD69-CD45RO+ Treg cells remained unchanged. The percentage of CTLA-4+ -expressing Treg cells transiently increased after 3 months of immunotherapy, whereas the percentage of FOXP3+ Treg cells did not change after 1 year of immunotherapy. Levels of IL-10+ cells transiently decreased after 3 months of immunotherapy. Four children who required inhaled fluticasone propionate administration for significant symptom worsening had no statistically significant increase in TGF-BETA1-secreting T cells at 12 months of SIT, in contrast to 12 children without inhaled corticosteroid treatment. The increase in TGF-BETA1-positive T cells only in children without significant symptom worsening requiring inhaled corticosteroid treatment limits the usefulness of TGF-BETA1 in monitoring response to allergen immunotherapy.

Decrease of FOXP3 mRNA in CD4+ T cells in latent autoimmune diabetes in adult

To study the percentage of peripheral blood CD4(+)CD25(+) T cells and the expression of FOXP3 mRNA in the patients with latent autoimmune diabetes in adult (LADA). Fresh peripheral blood samples were obtained from 60 patients with LADA, 30 patients with type 2 diabetes and 30 age- and sex-matched matched healthy nondiabetic control subjects without diabetic family history. Two-color staining (anti-CD4, anti-CD25, anti-CD3, and anti-CD8) flow cytometric analysis was employed to measure the CD4(+)CD25(+) T cells. The CD4 positive human cells were isolated with immunomagnetic beads, and then real time-PCR was used to test the expression of FOXP3 mRNA in the CD4(+) T cells. In the LADA group, the percentage of CD4(+)CD25(+) T cells was 4.1 +/- 1.9, significantly higher than that of the normal control group (2.8 +/- 1.5, P < 0.01), the ratio of CD4(+)CD25(+) to the CD4(+) T cells was 11.9 +/- 5.0, significantly higher than that of the normal control group (8.2 +/- 3.7, P < 0.01), the percentage CD8(+) T cells was 24.6 +/- 6.8, significantly higher than that of the normal control group (19.4 +/- 7.1, P < 0.01) and the CD4(+)/CD8(+) ratio was 1.5 +/- 0.5, significantly lower (1.9 +/- 0.6, P < 0.01). The expression of FOXP3 mRNA in CD4(+) T cells of the LADA group was 0.52 time that of the control group (P < 0.01). The CD4(+)/CD8(+) ratio of LADA group was significantly lower that of the type 2 diabetes group (1.8 +/- 0.8, P < 0.05), however, the other results were not significantly different between these 2 groups. The percentage of was positively correlated with the titer of glutamic acid decarboxylase antibody (GADA) (r = 0.292, P < 0.05). Though the percentage of CD4(+)CD25(+) T cells and the level of CD25 expression in CD4(+) T cells are elevated, the expression of FOXP3 mRNA in CD4(+) T cells is lower. in the patients with LADA. The regulatory T cells may have defective suppressor function in patients with LADA.

The study of CD4+CD8+、CD4+CD25+ regulative T cells in peripheral blood of patients with primary biliary cirrhosis and its association with the hepatic damnification

目的 检测原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者外周血CD4+CD8+T、CD4+CD25+调节性T细胞亚群,探讨其与肝功能损伤、抗AMA-M2抗体产生的关系.方法采用流式细胞术检测北京协和医院住院和门诊PBC患者(n=27)外周血CD4+CD8+T细胞、CD4+CD25+T细胞群比例,以26例其他肝脏疾病患者作为疾病对照组,30例健康体检者作为正常对照,观察调节性T细胞亚群与患者的肝功能指标及自身抗体如AMA-M2、ANA的关系.结果 PBC患者外周血CD4+CD25+T细胞比例与正常对照组比较结果差异无统计学意义(P>0.05),但显著高于其他肝脏疾病组(P<0.05).CD4+CD8+T细胞群与正常人相比结果差异无统计学意义,其他肝病组明显高于正常对照组(P<0.05).PBC患者外周血NK细胞比例显著低于正常对照组(P<0.05).肝功严重损伤的PBC患者外周血CD4+CD25+T细胞比例明显高于肝功能轻度损伤者(P<0.05).PBC患者外周血CD4+CD25+T细胞数量与肝功能损伤指标ALB呈负相关(r =-0.338,P<0.05),与TBIL、DBIL呈正相关(r分别为0.362,0.386,P<0.05).CD4+CD25+/CD4+比例与GGT呈负相关(r=-0.335,P<0.05),与TBIL、DBIL呈正相关(r分别为0.333,0.339,P<0.05).抗AMA-M2抗体阳性患者外周血CD4+CD25+细胞比例明显高于AMA-M2阴性患者(P<0.01).未发现CD4+CD25+T、CD4+CD8+T细胞比例在ANA+和ANA-PBC患者之间差异有统计学意义.结论 PBC患者外周血CD4+CD25+T细胞群比例与肝功能损害和抗AMA-M2抗体的产生密切相关,因此推测CD4+CD25+T细胞的变化可能是导致病情发展以及肝脏损伤的关键环节之一。

A Combination of Anergic Cells' Adoptive Transfer and Rapamycin Therapy Prolongs Cardiac Allograft Survival in Mice

The in vivo immunoregulatory effect of anergic cells induced by blocking the costimulatory pathway was investigated in this study. Anergic cells were generated in vitro by mixed culture of murine splenic cells from BALB/c and C3H/HeJ under the blockade of anti-CD154 and anti-CD80 monoclonal antibodies, and the in vitro activity of anergic cells were observed. The 3.0 Gy gamma-irradiated BALB/c mice received cardic allografts from C3H/HeJ, and anergic cells were intravenously injected immediately after transplantation. Recipient mice injected with anergic cells also received rapamycin therapy (1 mg/kg/day) for 14 days. On day 7 after transplantation, the subsets of peripheral blood T lymphocytes, the pathology of grafts and the infiltration of lymphocytes in grafts were analysed. Untreated gamma-irradiated animals showed a graft median survival time (MST) of 9 days. Animals injected with anergic cells only or receiving rapamycin therapy alone showed MST of 11 and 17 days, respectively. MST of allograft in mice treated with control cells plus rapamycin therapy was 9 days. Animals injected with anergic cells plus rapamycin therapy, but receiving third-party allografts (C57BL/6J), showed an MST of 15 days. However, anergic cell injection plus rapamycin therapy prolonged allograft survival significantly (MST 28 days, P < 0.01). The rejection was mild and tissue architecture was preserved in recipient mice receiving anergic cell injection plus rapamycin therapy. Furthermore, anergic cells and rapamycin therapy decreased the percentage of peripheral blood CD4+ and CD8+ T cells (including CD25+, CD152+, CD154+ and CD28+ subsets) and greatly reduced the infiltrating lymphocytes in allografts (including CD3+, CD4+, CD8+ and CD25+ T cells). In conclusion, the treatment based on anergic cells' adoptive transfer plus rapamycin therapy demonstrated a significant prolongation of murine cardiac allograft survival in a donor antigen-specific manner. This therapeutic protocol alleviated allograft rejection to solid allograft in vivo.

Predominant T H1 cytokine pattern in peripheral blood from subjects with chronic obstructive pulmonary disease

Background: Previous studies have provided evidence for an inflammatory process in the large airways of subjects with chronic obstructive pulmonary disease (COPD), consisting predominantly of activated T cells. No data are available on the T H1 /T H2 T-cell cytokine pattern in this disease. Objective: We sought to characterize the T H1 /T H2 T-cell cytokine pattern in subjects with COPD. Methods: We examined the IFN-γ and IL-4 expression in peripheral blood CD4+ and CD8+ T cells from 20 patients with COPD and 25 control subjects by using a flow cytometric method of intracellular cytokine detection. We also examined the expression of 2 surface activation markers (CD25 and HLA-DR) on peripheral blood CD4+ and CD8+ T cells. Results: There was an increased percentage of IFN-γ–producing cells (30.3% [range, 12.9% to 60.4%] vs 19.1% [range, 4% to 31.2%], P = .003) and a decreased percentage of IL-4–producing cells (4.55% [range, 0.6% to 11.3%] vs 9.5% [2.1% to 21.3%], P = .0008) among peripheral blood CD4+ T cells from the patients with COPD compared with control subjects. There was no significant difference between the 2 groups in the percentage of peripheral blood CD8+ T cells producing IFN-γ or IL-4 or in the percentage of peripheral blood CD4+ and CD8+ T cells expressing CD25 and HLA-DR. Conclusion: These findings provide evidence for a T H1 -like immune response of peripheral blood CD4+ T cells in subjects with COPD. (J Allergy Clin Immunol 1999;103:458-62.)

Neurokinin type-1 receptor antagonist inhibits enhancement of T cell functions by substance P in normal and neuromanipulated capsaicin-treated rats

Substance P (SP) plays a major role in the regulation of the interaction between immune and nervous systems. SP administration stimulates Con A-induced proliferation of spleen and peripheral blood lymphocytes from normal and neonatally capsaicin treated rats, which correlated with enhanced IL-2 production and expression of activation antigens such as IL-2 receptor α chain (CD25) and RT1B MHC class II molecule. Moreover, SP markedly increased the percentage of CD5 + and CD4 + T lymphocytes in the peripheral blood of capsaicin-treated rats. Concomitant administration of SP with the non-peptide Neurokinin-1 receptor (NK 1R) antagonist SR140333 completely inhibited the SP-mediated augmentation of Con A-induced PBL proliferation and IL-2 production as well as of CD4 + CD25 + and CD4 + RT1B + T cell numbers in normal and capsaicin-treated rats. SR 140333 also blocked the increased percentage of peripheral blood CD4 + T cells induced by SP in capsaicin-treated rats.

CD4+/Leu-7+ LARGE GRANULAR LYMPHOCYTES IN LONG-TERM RENAL ALLOGRAFT RECIPIENTS A SUBSET OF ATYPICAL T CELLS1

In long-term renal allograft recipients on conventional immunosuppression, we have previously reported an abnormal expansion of CD3+/Leu-7+ cells. These cells are large granular lymphocytes without any natural killer activity. About 20% of these CD3+/Leu-7+ cells coexpress the CD4 differentiation antigen. In 65 transplant recipients at risk for more than 6 months, the mean percentage of peripheral blood CD4+/Leu-7+ cells is significantly increased compared with 34 normals (5.0 +/- 0.6% versus 1.0 +/- 0.1%, P less than 0.0001). Patients who never received azathioprine do not show such an abnormality. We carried out this study to further define the phenotype, morphology, and function of these cells. As to phenotype, they coexpress CD2, CD3 but do not coexpress CD1, CD8, CD11, CD16, CD19, CD25, HLA-DR, Leu-M3. Morphologically, CD4+/Leu-7+ cells are typical large granular lymphocytes undistinguishable from CD16+ effector NK cells. CD4+/Leu-7+ cells do not exhibit any natural killer cell activity. In contrast to CD4+/Leu-7- cells, CD4+/Leu-7+ cells do not proliferate when stimulated with either lectins (Con A, PHA) or allogeneic cells. When stimulated for 3 days with PHA, sorted CD4+/Leu-7+ cells do not express IL-2 receptors as detected with a PE-conjugated anti-CD25 monoclonal antibody, whereas 40% of CD4+-Leu-7- cells do so. Finally, when stimulated with PHA, CD4+-Leu-7+ cells are not able to produce detectable levels of IL-2, while CD4+-Leu-7- cells do so. In long-term renal allograft recipients on conventional immunosuppression, Leu-7 antigen identifies a subset of CD4+ cells that do not behave like regular T helper cells. We speculate that these cells represent an alteration in the cellular environment in transplant recipients, perhaps leading to long-term complications such as cancers and chronic viral infections.