Peripheral Blood T-cell Subsets Research Articles

Relationship between T-lymphocyte subsets in peripheral blood and acute rejection after liver transplantation in rats

Relationship between T-lymphocyte subsets in peripheral blood and acute rejection after liver transplantation in rats

CD4+CD62L+ Central Memory T Cells Can Be Converted to Foxp3+ T Cells

The peripheral Foxp3+ Treg pool consists of naturally arising Treg (nTreg) and adaptive Treg cells (iTreg). It is well known that naive CD4+ T cells can be readily converted to Foxp3+ iTreg in vitro, and memory CD4+ T cells are resistant to conversion. In this study, we investigated the induction of Foxp3+ T cells from various CD4+ T-cell subsets in human peripheral blood. Though naive CD4+ T cells were readily converted to Foxp3+ T cells with TGF-β and IL-2 treatment in vitro, such Foxp3+ T cells did not express the memory marker CD45RO as do Foxp3+ T cells induced in the peripheral blood of Hepatitis B Virus (HBV) patients. Interestingly, a subset of human memory CD4+ T cells, defined as CD62L+ central memory T cells, could be induced by TGF-β to differentiate into Foxp3+ T cells. It is well known that Foxp3+ T cells derived from human CD4+CD25- T cells in vitro are lack suppressive functions. Our data about the suppressive functions of CD4+CD62L+ central memory T cell-derived Foxp3+ T cells support this conception, and an epigenetic analysis of these cells showed a similar methylation pattern in the FOXP3 Treg-specific demethylated region as the naive CD4+ T cell-derived Foxp3+ T cells. But further research showed that mouse CD4+ central memory T cells also could be induced to differentiate into Foxp3+ T cells, such Foxp3+ T cells could suppress the proliferation of effector T cells. Thus, our study identified CD4+CD62L+ central memory T cells as a novel potential source of iTreg.

The co-receptor BTLA negatively regulates human Vγ9Vδ2 T-cell proliferation: a potential way of immune escape for lymphoma cells

AbstractVγ9Vδ2 cells, the major γδ T-cell subset in human peripheral blood, represent a T-cell subset that displays reactivity against microbial agents and tumors. The biology of Vγ9Vδ2 T cells remains poorly understood. We show herein that the interaction between B- and T-lymphocyte attenuator (BTLA) and herpesvirus entry mediator (HVEM) is a major regulator of Vγ9Vδ2 T-cell proliferation control. BTLA was strongly expressed at the surface of resting Vγ9Vδ2 T cells and inversely correlated with T-cell differentiation. BTLA-HVEM blockade by monoclonal antibodies resulted in the enhancement of Vγ9Vδ2 T-cell receptor–mediated signaling, whereas BTLA-HVEM interaction led to a decrease in phosphoantigen-mediated proliferation by inducing a partial S-phase arrest. Our data also suggested that BTLA-HVEM might participate in the control of γδ T-cell differentiation. In addition, the proliferation of autologous γδ T cells after exposition to lymphoma cells was dramatically reduced through BTLA-HVEM interaction. These data suggest that HVEM interaction with BTLA may play a role in lymphomagenesis by interfering with Vγ9Vδ2 T-cell proliferation. Moreover, BTLA stimulation of Vγ9Vδ2 T cells appears as a new possible mechanism of immune escape by lymphoma cells.

Immune restoration after antiretroviral therapy: the pitfalls of hasty or incomplete repairs.

Antiretroviral therapy (ART) is a life-saving intervention in human immunodeficiency virus (HIV) infection. Immune restoration after ART dramatically reduces the incidence and severity of opportunistic diseases and death. On some occasions, immune restoration may be erratic, leading to acute inflammatory responses (known as immune reconstitution inflammatory syndrome) shortly after ART initiation, or incomplete, with residual inflammation despite chronic treatment, leading to non-infectious morbidity and mortality. We propose that ART may not always restore the perfect balance of innate and adaptive immunity in strategic milieus, predisposing HIV-infected persons to complications of acute or chronic inflammation. The best current strategy for fully successful immune restoration is early antiretroviral therapy, which can prevent acquired immunodeficiency syndrome (AIDS)-associated events, restrict cell subset imbalances and dysfunction, while preserving structural integrity of lymphoid tissues. Future HIV research should capitalize on innovative techniques and move beyond the static study of T-cell subsets in peripheral blood or isolated tissues. Improved targeted therapeutic strategies could stem from a better understanding of how HIV perturbs the environmental niches and the mobility and trafficking of cells that affect the dynamic cell-to-cell interactions and determine the outcome of innate and adaptive immune responses.

Peripheral and tumor immune correlates in patients with advanced melanoma treated with combination nivolumab (anti-PD-1, BMS-936558, ONO-4538) and ipilimumab.

3003^ Background: Nivolumab and ipilimumab are fully human monoclonal antibodies that block the immune checkpoint receptors PD-1 and CTLA-4, respectively. In a multi-cohort, phase I study of nivolumab/ipilimumab combination therapy in melanoma patients (pts), objective response rates up to 47% were observed (NCT01024231). Putative predictive biomarkers from peripheral blood (PB) or tumor, including tumor PD-L1 expression, absolute lymphocyte count (ALC) and PB myeloid derived suppressor cells (MDSC) were evaluated. Pharmacodynamic changes in activated and effector T cells were also assessed. Methods: Tumor PD-L1 membrane expression was assessed in archival FFPE specimens by immunohistochemistry (28-8 PD-L1 antibody). ALC was measured in serial PB samples; changes in the percentage, number and phenotype of activated CD4+ and CD8+T cells and MDSC were characterized by flow cytometry. Results: PD-L1 expression was seen in 37% (10/27) of pts, using a cut-off of 5% tumor cell membrane staining. Objective responses (OR) were seen in pts with both PD-L1 negative (8/17) and PD-L1 positive (4/10) tumors. Relative to baseline, a rise in ALC was not detected, but phenotypic changes in PB T-cell subsets, including increases in the percentage of CD4 and CD8 expressing HLA-DR, ICOS and/or Ki67 were seen with combination therapy. Low ALC (<1.0 at wk 6-7) did not preclude OR as 3 of 12 pts with low ALC responded. Of pts evaluated, OR with ≥80% reduction in tumor burden at 12 wk were seen in pts with a low frequency of pretreatment PB MDSC (3/7) but no OR were seen in pts with high MDSC (0/6). Conclusions: In this small subset of pts,OR were seen independent of PD-L1 or ALC status in contrast to prior observations with nivolumab or ipilimumab, respectively. Thus, the immune response generated by combination therapy may have unique features compared to either monotherapy. The relationship between frequency of PB MDSC and reduction in tumor burden will be further explored. Further efforts in this study and in future phase III randomized studies will investigate these and other phenotypic changes in immune cell populations and their relationship to patterns of clinical activity. Clinical trial information: NCT01024231.

Kinetics of functionally distinct T-lymphocyte subsets in heart transplant recipients after induction therapy with anti-CD25 monoclonal antibodies

T cells are involved in the maintenance of immunocompetence and in the development of alloimmune responses in solid organ transplant recipients. The kinetics of functionally distinct T-cell subsets in peripheral blood has received little attention in the field of heart transplantation. We performed a simultaneous analysis of the maturation, activation, and regulatory profiles of T cells using 4-color flow cytometry in a study of 77 heart recipients. Induction therapy included 2 doses of anti-CD25 monoclonal antibodies (daclizumab). Lymphocyte subsets were prospectively evaluated at different times before and up to 1year after transplantation in 46 heart recipients. A separate cross-sectional study was performed in 33 heart recipients who had received a transplant more than 1year previously to evaluate abnormalities persisting in the long term. As compared with baseline values, a decrease in regulatory CD4+ T-cell percentages (CD4+CD127lowCD25highFoxP3+) was observed from day 7 to 12months after transplantation. Interestingly, T cells expressing the beta chain of IL-2 (CD122+) remained stable during the first 3months. A significant decrease in the activation status of CD4 T cells was documented from day 7 to 1year after transplantation, while the activation status of CD8+ T cells remained stable during follow-up. Compared with values for healthy controls (n=36), higher CD8+ terminally differentiated effector memory percentages (CD8+CD45RA+CCR7−) were observed from baseline up to more than 1year after transplantation. Rejection was associated with higher levels of these cells during the first 6months after transplant. We characterized the abnormalities in distinct functional T-cell subsets at different times before and after heart transplantation. Some of these abnormalities should be further investigated as biomarkers of clinical complications.

Effects of sodium selenite on the decreased percentage of T cell subsets, contents of serum IL-2 and IFN-γ induced by aflatoxin B1 in broilers

Aflatoxin B1 (AFB1), especially inducing hepatocellular carcinoma and immunosuppression of animals, poses a serious healthy and economic hazard to both humans and livestock. Animal studies have demonstrated that selenium (Se) provides anticarcinogenic and antimutagenic effects against AFB1. However, the effects of Se against AFB1-induced immunosuppression were rarely reported. To test this, three hundred 1-day-old male avian broilers were divided into five groups and fed on control diet (0.4mg/kg Se), AFB1 group(0.3mg/kg AFB1+0.4mg/kg Se), AFB1+Se group I(0.3mg/kg AFB1+0.6mg/kg Se), AFB1+Se group II(0.3mg/kg AFB1+0.8mg/kg Se) and AFB1+Se group III(0.3mg/kg AFB1+1.0mg/kg Se) for 21days (n=60/group). Although the body weight in AFB1 group was lower than that in control group at 14days of age, there no significant differences on body weight among five groups at 7 and 21days of age. No evident clinical symptoms were observed among five groups from 7 to 21days of age. The percentages of peripheral blood CD3+, CD3+CD4+, CD3+CD8+ and the contents of serum IL-2 and IFN-γ in AFB1 group were decreased, compared with those in control group. Compared with those in AFB1 group, the percentages of CD3+, CD3+CD4+ and CD3+CD8+ T cells in three AFB1+Se groups were increased from 14 to 21days of age, and the contents of serum IL-2 and IFN-γ in all AFB1+Se groups were increased from 7 to 21days of age. On the contrary, the percentages of CD3+, CD3+CD4+ and CD3+CD8+ T cells, and the contents of Serum IL-2 and IFN-γ in AFB1+Se group III were lower than those in AFB1+Se group II. It was concluded that 0.6 and 0.8mg/kg Se could increase the decreased percentages of peripheral blood T-cell subsets and the contents of serum IL-2 and IFN-γ induced by 0.3mg/kg AFB1 in the diets, and cellular immune function could be improved in chickens.

Association Between Telomere Length and Experimentally Induced Upper Respiratory Viral Infection in Healthy Adults

Although leukocyte telomere length is associated with mortality and many chronic diseases thought to be manifestations of age-related functional decline, it is not known whether it relates to acute disease in younger healthy populations. To determine whether shorter telomeres in leukocytes, especially CD8CD28- T cells, are associated with decreased resistance to upper respiratory infection and clinical illness in young to midlife adults. Between 2008 and 2011, telomere length was assessed in peripheral blood mononuclear cells (PBMCs) and T-cell subsets (CD4, CD8CD28+, CD8CD28-) from 152 healthy 18- to 55-year-old residents of Pittsburgh, Pennsylvania. Participants were subsequently quarantined (single rooms), administered nasal drops containing a common cold virus (rhinovirus 39), and monitored for 5 days for development of infection and clinical illness. Infection (virus shedding or 4-fold increase in virus-specific antibody titer) and clinical illness (verified infection plus objective signs of illness). Rates of infections and clinical illness were 69% (n = 105) and 22% (n = 33), respectively. Shorter telomeres were associated with greater odds of infection, independent of prechallenge virus-specific antibody, demographics, contraceptive use, season, and body mass index (PBMC: odds ratio [OR] per 1-SD decrease in telomere length, 1.71 [95% CI, 1.08-2.72]; n = 128 [shortest tertile 77% infected; middle, 66%; longest, 57%]; CD4: OR, 1.76 [95% CI, 1.15-2.70]; n = 146 [shortest tertile 80% infected; middle, 71%; longest, 54%]; CD8CD28+: OR, 1.93 [95% CI, 1.21-3.09], n = 132 [shortest tertile 84% infected; middle, 64%; longest, 58%]; CD8CD28-: OR, 2.02 [95% CI, 1.29-3.16]; n = 144 [shortest tertile 77% infected; middle, 75%; longest, 50%]). CD8CD28- was the only cell population in which shorter telomeres were associated with greater risk of clinical illness (OR, 1.69 [95% CI, 1.01-2.84]; n = 144 [shortest tertile, 26%; middle, 22%; longest, 13%]). The association between CD8CD28- telomere length and infection increased with age (CD8CD28- telomere length × age interaction, b = 0.09 [95% CI, 0.02-0.16], P = .01, n = 144). In this preliminary study among a cohort of healthy 18- to 55-year-olds, shorter CD8CD28- T-cell telomere length was associated with increased risk for experimentally induced acute upper respiratory infection and clinical illness.

P671 An IL23R risk variant is associated with changes in CD4+ T-cell subsets in peripheral blood of Crohn's disease patients

Methods: 93 IBD patients with normal TPMT activity and wild-type genotype treated with thiopurines were included. Case group: patients with thiopurine-induced myelotoxicity and without other thiopurine-induced adverse effect. Control group: patients without thiopurine-induced side effects consecutively included. TPMT activity over 13.7 UI/mL was considered normal. DNA was extracted from peripheral blood nucleated cells. TPMT genotype was determined by sequencing (TPMT*2, *3A, *3B, *3C, *3D, *4, *5, *6, *7, *9, *10, *15, *16, *19 and *22 alleles). Myelotoxicity was defined as <3,000/ml leucocytes, <1,500/ml neutrophils, or <100,000/ml platelets. Genomic DNA was analysed using Illumina OmniExpress Exome BeadChip genotyping array. This array interrogates a total of 951,117 SNPs (660K common and 200k rare coding variants). Genotype calls were generated using Illumina GenomeStudio. After standard QC control, associations between SNPs and myelotoxicity were assessed using logistic regression analysis. Results: 93 patients were included (37 cases and 56 controls). The distribution of gender, type of IBD, mean age, mean TPMT activity and mean dose of mercaptopurine (1.3 vs. 1.4mg/kg) were similar between cases and controls. The percentage of patients with mercaptopurine was higher among cases (32.4 vs. 12.5%, p = 0.02), while mean azathioprine dose was slightly higher among controls (2.2 vs. 2.5mg/kg, p = 0.03). A total of four SNPs showed significant association: SNP1: p = 6.5×10 5, OR = 10.4 (2.5 21); SNP2: p = 6.6×10 5, OR = 6.2 (2.4 12); SNP3: p = 8.5×10 5, OR = 0.1 (0.07 0.5); and SNP4: p = 8.8×10 5, OR = 0.2 (0.1 0.4). The SNP1 is located close to a gene that encodes a relevant enzyme of the thiopurine metabolic pathway. Conclusions: An exome-wide association study identified four new SNPs that could explain thiopurine-induced toxicity not related to TPMT deficiency. The SNP with the strongest association could regulate the expression of an enzyme of the thiopurine metabolic pathway. Although further validation is required, these variants could be promising genetic predictors of thiopurine-induced myelotoxicity.

CCR6 Is Required for Epidermal Trafficking of γδ-T Cells in an IL-23-Induced Model of Psoriasiform Dermatitis

A subset of CCR6+, γδ-low (GDL) T cells that express Th17 cytokines in mouse skin participates in IL-23-induced psoriasisform dermatitis. We use CCR6-deficient (KO) and wildtype (WT) mice to analyze skin trafficking patterns of GDL T cells and function-blocking mAbs to determine the role of CCR6 in IL-23-mediated dermatitis. Herein, CCL20 was highly upregulated in IL-23-injected WT mouse ear skin as early as 24 hours after initial treatment, and large numbers of CCR6+ cells were observed in the epidermis of IL-23-injected WT mice. Anti-CCL20 mAbs reduced psoriasiform dermatitis and blocked recruitment of GDL T cells to the epidermis. In CCR6 KO mice, GDL T cells failed to accumulate in the epidermis after IL-23 treatment, but total numbers of GDL T cells in the dermis of WT and CCR6 KO mice were equivalent. There was a ~70% reduction in the proportion of IL-22+ GDL T cells in the dermis of CCR6 KO mice (vs. WT mice), suggesting that effector function as well as epidermal recruitment of GDL T cells are impaired in CCR6-deficient mice. Thus, these data show CCR6 regulates epidermal trafficking of γδ T cell subsets in skin and suggest the potential of CCR6 as a therapeutic target for psoriasis.

Association of CD8 T Cells with Depression and Anxiety in Patients with Liver Cirrhosis

Depression and anxiety frequently co-occur in patients with. cirrhosis, but their underlying biological substrates are unclear. There is now evidence to suggest that depression is accompanied by signs of an immune response. This study investigated the correlation between depression/anxiety and T-lymphocyte subsets in liver cirrhosis patients. A total of 59 patients (37 males and 22 females; aged between 26-81 years) with cirrhosis were enrolled in the study. Severity of depression and anxiety were assessed through the Hamilton depressive scale (HAMD, the 24-item version) and the Hamilton anxiety scale (HAMA). T-lymphocyte subsets (CD3, CD4, and CD8) in peripheral blood were determined by flow cytometry. The relationship between lymphocyte subsets and depression/anxiety scores was studied by correlation analysis. The mean total HAMD and HAMA scores for the 59 subjects were 12.8 +/- 10.4 (range = 0-46) and 7.0 +/- 5.7 (range = 0-26), respectively. Fourteen of 59 subjects (23.7%) had HAMD scores equal to or above 20, indicative of depression. The percentage of CD8, but not CD3 or CD4, in T-lymphocyte subsets was positively correlated with depression (HAMD) (r = 0.268, P = 0.043) and anxiety severity (HAMA) (r = 0.321, P = 0.013). After controlling for age and Child-Pugh scores, the correlations were still significant. Around one-fourth of cirrhosis patients may have depression, although depression is not related to cirrhosis severity. Our findings are the first to show that depression and anxiety may be associated with increased levels of CD8 in T-lymphocyte subsets in cirrhosis patients, suggesting that an imbalance of T-lymphocyte subsets may be a factor facilitating depression and anxiety in cirrhotic patients. Examination of CD8 T-lymphocytes may prove useful in assessing the potential relationship between depression, anxiety, immunity, and liver cirrhosis.

A randomized controlled trial comparing total glucosides of paeony capsule and compound glycyrrhizin tablet for alopecia areata

To observe the efficacy and safety of total glucosides of paeony capsule (TGPC) in patients with mild and moderate alopecia areata. A total of 86 outpatients were randomly allocated into two groups of TGPC (treatment, 44 cases) and compound glycyrrhizin tablet (control, 42 cases). The treatment group was given oral TGPC, three times daily and 600 mg per time; the control group was given oral compound glycyrrhizin tablets, three times daily and 50 mg per time. In addition, both groups were given 10 mg of vitamin B(2) and tapped the bold patches with massage. The treatment course was three months for both groups. Peripheral blood T-cell subsets (CD3(+)CD4(+), CD3(+)CD8(+), Th, Ts, Th/Ts) of 10 patients randomly selected from each group respectively were tested before and after three months of treatment. The effectiveness and adverse reaction of all cases were observed each month. The safety was evaluated according to the incidence rate of adverse reaction. In the treatment group, the cured and markedly effective rate was 36.36% (16/44), 50.00% (22/44) and 68.18% (30/44) at the end of first, second and third month of treatment, respectively, and the incidence rate of adverse reaction was 13.64% (6/44). In the control group, the cured and markedly effective rate was 38.10% (16/42), 57.14% (24/42) and 71.43% (30/42), respectively, and the incidence rate of adverse reaction was 16.67% (7/42). The cured and markedly effective rate and the incidence rate of adverse reaction were similar in both groups (P>0.05). TGPC and compound glycyrrhizin tablet can inhibit CD3(+)CD4(+) and CD3(+)CD8(+), and decrease the ratio of Th/Ts (P<0.05). TGPC is effective and safe in the treatment of alopecia areata.

Expression of CD30 in patients with acute graft-versus-host disease

AbstractAcute GVHD (aGVHD) remains a major source of morbidity after allogeneic hematopoietic cell transplantation. CD30 is a cell-surface protein expressed on certain activated T cells. We analyzed CD30 expression on peripheral blood T-cell subsets and soluble CD30 levels in 26 patients at the time of presentation of aGVHD, before the initiation of treatment, compared with 27 patients after hematopoietic cell transplantation without aGVHD (NONE). Analysis by flow cytometry showed that patients with aGVHD had a greater percentage of CD30 expressing CD8+ T cells with the difference especially pronounced in the central memory subset (CD8+CD45RO+CD62L+): GVHD median 12.4% (range, 0.8%-33.4%) versus NONE 2.1% (0.7%, 17.5%), P < .001. There were similar levels of CD30 expression in naive T cells, CD4+ T cells, and regulatory (CD4+CD127lowCD25+) T cells. Plasma levels of soluble CD30 were significantly greater in patients with GVHD: median 61.7 ng/mL (range, 9.8-357.1 ng/mL) versus 17.4 (range, 3.7-142.4 ng/mL) in NONE (P < .001). Immunohistochemical analysis of affected intestinal tissue showed many CD30+ infiltrating lymphocytes present. These results suggest that CD30 expression on CD8+ T-cell subsets or plasma levels of soluble CD30 may be a potential biomarker for aGVHD. CD30 may also represent a target for novel therapeutic approaches for aGVHD.

The impact of terminal complement blockade on the efficacy of induction with polyclonal rabbit antithymocyte globulin in living donor renal allografts

BackgroundEculizumab, a potent inhibitor of terminal complement activation, appears promising in reducing early antibody-mediated rejection in positive crossmatch kidney transplantation. However, its concomitant use with polyclonal rabbit antithymocyte globulin (rATG) might reduce the efficacy of rATG. This study aimed to evaluate the effect of eculizumab on the efficacy of rATG in vivo and determine the role of complement in rATG-induced lymphocyte cell depletion. Patients and methodsThirty-six kidney transplant recipients were classified into 3 groups according to induction regime: anti-IL-2 receptor antibody alone induction group (basiliximab, n=8); rATG induction (n=20), and rATG+eculizumab induction group (n=8). Peripheral blood T-cell subsets and NK cells were measured 3–4days after transplant (after 3 doses of rATG). ResultsCompared to anti-IL-2 receptor antibody induction group, both groups treated with rATG demonstrated significant depletion of all T-cell subsets (CD3-positive cells) (P<0.0001 for rATG vs. anti-IL-2 receptor antibody induction group; P<0.001 for rATG+eculizumab vs. anti-IL-2 receptor antibody group). However, while T-cell counts were low in all rATG-treated patients, eculizumab treatment resulted in higher peripheral blood T-cell counts in rATG treated patients (P=0.005). Before induction, median total lymphocyte counts were normal for the three study groups. By 1, 4months and 1year, median the total lymphocyte count was normal for the anti-IL-2 receptor antibody group but was below normal range or at the lower edge of normality for rATG and rATG+eculizumab groups. ConclusionsThis small-sample size study suggests that peripheral T cells are depleted by rATG in the presence of terminal complement inhibition. However, eculizumab appears to have a mild inhibitory effect on peripheral blood T-cell depletion by rATG in kidney transplant recipients.

Effect of Methionine Deficiency on the Thymus and the Subsets and Proliferation of Peripheral Blood T-Cell, and Serum IL-2 Contents in Broilers

The purpose of this study was to investigate the effects of methionine deficiency on cellular immune function by determining morphological and ultrastructural changes of thymus, thymic cell cycle and apoptosis, peripheral blood T-cell subsets, T-cell proliferation function and the serum interleukin-2 (IL-2) contents. 120 1-d-old broilers were randomly divided into two groups (6 replicates in each group and 10 broilers in each replicate) and fed on a control diet or methionine deficient diet for 42 d. Lesions were observed in experiment. Histopathologically, lymphopenia and congestion were observed in the medulla of thymic lobule. Ultrastructurally, there were more apoptosis lymphocytes, and the mitochondria of lymphocytes were swelled in thymus of methionine deficiency. The G0/G1 phase of the cell cycle of the thymus was much higher (P<0.01), and the S, G2+M phases and proliferating index (PI) were lower (P<0.01) in methionine deficiency than in control group. And the percentage of apoptotic cells in the thymus was significantly increased in methionine deficiency (P<0.01). The percentage of CD4+ and CD8+ T-cells was decreased in methionine deficiency compared with control group. Meanwhile, the proliferation function of peripheral blood T-cell was decreased in methionine deficiency. Also, the serum IL-2 contents were decreased in methionine deficiency. It was concluded that methionine deficiency could cause pathological and ultrastructural changes of thymus, reduce the T-cell population, serum IL-2 contents and the proliferation function of T-cells, and induce increased percentage of apoptotic cells. The cellular immune function was finally impaired in broilers.

Cytokine-induced killer (CIK) cell therapy for patients with hepatocellular carcinoma: efficacy and safety

PurposeTo evaluate the efficacy of cytokine-induced killer (CIK) cell therapy in the treatment of hepatocellular carcinoma.Materials and methodsRandomized phase II and III trials on CIK cell-based therapy were identified by electronic searches using a combination of "hepatocellular carcinoma" and "cytokine-induced killer cells".ResultsThe analysis showed significant survival benefit (one-year survival, p < 0.001; two-year survival, p < 0.001; median overall survival, p < 0.001) in favor of CIK-based therapy. Comparison of CIK group versus non-CIK group resulted in a significantly prolonged progression-free survival (PFS) (p < 0.01). A favored disease control rate (DCR) and overall response rate (ORR) were also observed in patients receiving CIK cell therapy (p < 0.01). Meanwhile, patients in the CIK group showed better quality of life (QoL), diminished HBV-DNA content and AFP level (p < 0.01). Comparing T-lymphocyte subsets in peripheral blood, the analysis showed the ratio of CD3+, CD4+, CD4+CD8+ and CD3+CD4+ T cells significantly increased in the CIK group, compared with the non-CIK group (p < 0.01).ConclusionsCIK cell therapy demonstrated a significant superiority in prolonging the median overall survival, PFS, DCR, ORR and QoL of HCC patients. These results support further larger scale randomized controlled trials for HCC patients with or without the combination of other therapeutic methods.

Frequency of T Cell Expressing Th1 and Th2 Associated Chemokine Receptor in Patients With Renal Allograft Dysfunction

Acute rejection of human renal allografts is a frequent, serious posttransplantation complication, occurring in up to 50% of recipients. Leukocyte recruitment is a central feature of acute allograft rejection. Chemokine receptors are expressed on leukocytes in a cell type–specific manner. Recently CCR5+ and CXCR3+ cells have been observed in allograft biopsy specimens of patients undergoing acute cellular rejection (ACR). Herein we investigated the expression of Th1 (CCR5, CXCR3, and CCR2) and Th2 (CCR4, CCR3, and CCR8)–associated chemokine receptors on CD4 and CD8 T-cell populations. We sought to correlate chemokine receptor expression in peripheral blood T-cell subsets with the types of graft dysfunction (biopsy-proven rejections). In the peripheral blood CD4+ and CD8+ T-cell populations of patients with graft dysfunction, we observed a high frequency of Th1-associated chemokine receptors CCR5+ and CCR2+ but not CXCR3.

Adaptive Immunity in Ankylosing Spondylitis: Phenotype and Functional Alterations of T-Cells before and during Infliximab Therapy

Our aim was to assess the phenotype of T-cell subsets in patients with ankylosing spondylitis (AS), a chronic inflammatory rheumatic disease. In addition, we also tested short-term T-cell activation characteristics. Measurements were done in 13 AS patients before and during the intravenous therapy with anti-TNF agent infliximab (IFX). Flow cytometry was used to determine T-cell subsets in peripheral blood and their intracellular signaling during activation. The prevalence of Th2 and Th17 cells responsible for the regulation of adaptive immunity was higher in AS than in 9 healthy controls. Although IFX therapy improved patients' condition, immune phenotype did not normalize. Cytoplasmic and mitochondrial calcium responses of CD4+ and CD8+ cells to a specific activation were delayed, while NO generation was increased in AS. NO generation normalized sooner upon IFX than calcium response. These results suggest an abnormal immune phenotype with functional disturbances of CD4+ and CD8+ cells in AS.

Lesions of thymus and decreased percentages of the peripheral blood T-cell subsets in chickens fed on diets excess in selenium

Selenium is an essential trace element possessing immune-stimulatory properties. The purpose of this 42-day study was to investigate the effects of excess dietary selenium on cellular immune function by determining morphological changes of thymus and peripheral blood T-cell subset. Three hundred 1-day-old avian broilers were fed on a basic diet (0.2 mg/kg selenium) or the same diet amended to contain 1, 5, 10, 15 mg/kg selenium supplied as sodium selenite (n = 60/group). Pathological lesions were progressed with the dietary Se level increased. Grossly, the volume of thymus was decreased. Histopathologically, lymphopenia and congestion were observed. Ultrastructurally, mitochondria injury was observed. In comparison with that of control group, 5, 10 and 15 mg/kg dietary Se decreased the percentage of CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) T cells of the peripheral blood, as measured by flow cytometry. The results showed that excess selenium (more than 5 mg/kg) intake could cause lesions of thymus and decrease of T-cell subsets. The cellular immune function was finally impaired in broilers.

Effect of oral scorpio and scolopendra powder on T-cell subsets in peripheral blood and intestine from rats with collagen induced arthritis

To observe effect of oral scorpio and scolopendra powder on T-cell subsets in peripheral blood and intestine from rats with collagen induced arthritis (CIA). 60 rats were randomly divided into 6 groups: normal control group, model control group, low-dose scorpio and scolopendra group, middle-dose scorpio and scolopendra group, high-dose scorpio and scolopendra group, and type II collagen group. Rat's rheumatoid arthritis was induced by collagen II (C II). Level of T-cell subsets from peripheral blood and intestine was measured by flow cytometry. CD4+ T cellular level was obviously increased (P < 0.05 or P < 0.01) or kept increased tendency in peripheral blood and intestine from the model group compared with that of the normal group, while the ratio of CD4+/CD8+ in intestine was obviously descent but the contrary in peripheral blood (P < 0.05 or P < 0.01). CD4+, CD8+ T cellular level in intestine were obviously descent and the ratio of CD4+ /CD8+ increased in all treated groups when compared with in the model group (P < 0.05 or P < 0.01). However, CD4+ T cellular level and the ratio of CD4+/CD8+ in peripheral blood were remarkablely decreased. The mechanism that scorpio and scolopendra could treat rat's rheumatoid arthritis may be regulating balance of T-lymphocyte subsets in peripheral blood and intestine.