Percentage Of HLA-DR Research Articles

Activation and Cell Cycle Antigens in CD4+and CD8+T Cells Correlate with Plasma Human Immunodeficiency Virus (HIV‐1) RNA Level in HIV‐1 Infection

The relationship between T cell activation and human immunodeficiency virus type 1 (HIV-1) replication was studied in HIV-infected subjects, 20 with and 10 without anti-HIV treatment. Expression of Ki-67 proliferation-associated antigen was increased in CD4+ and CD8+ T cells and correlated with HLA-DR. In subjects without anti-HIV treatment, the plasma HIV-1 RNA level correlated with HLA-DR in CD4+ T cells, with Ki-67 in CD8+ T cells, and with expression of CD38 in both T cell subsets. A proportion of treated subjects had increased T cell activation despite 4 months of highly active antiretroviral treatment (HAART). In subjects receiving HAART, a high percentage of HLA-DR+ CD4+ T cells was associated with signs of opportunistic infections. This work supports the concept that, in the natural course of HIV-1 infection, HIV replication itself leads to general T cell activation and that opportunistic infections generate additional CD4+ T cell activation and HIV replication.

Alloantigen presenting capacity, T cell alloreactivity and NK function of G-CSF-mobilized peripheral blood cells.

In this study we addressed whether the proportion and the function of antigen presenting cells (APC), T and NK lymphocytes are modified in the apheresis product of six healthy donors who received a stem cell mobilizing treatment with glycosylated G-CSF at 10 microg/kg/day x 5 days s.c. Flow cytometry analysis showed comparable percentages of HLA-DR+, CD19+, CD86+, CD80+ and CD1a+ cells in preG-CSF-peripheral blood mononuclear cells (preG-PBMC) and after mobilization in G-PBMC, whereas the proportion of CD14+ monocytes significantly increased in G-PBMC (3+/-1% vs 17+/-8%, P = 0.003). Analysis of lymphocyte subsets in preG-PBMC and G-PBMC showed similar proportions of CD3+, CD4+, CD8+ and CD28+ T cells, but a significantly lower percentage of CD16+ (11+/-7% vs 4+/-1%, P=0.01), CD56+ (15+/-6% vs 5+/-2%, P= 0.008), CD57+ (16+/-9% vs 5+/-2%, P=0.04), CD25+ (19+/-2% vs 9+/-6%, p=0.009) and CD122+ (5+/-2% vs 2+/-1%, P = 0.05) cells in G-PBMC. Unfractionated preG-PBMC and G-PBMC were irradiated and tested in primary mixed leukocyte culture (MLC) with two HLA-incompatible responders and induced efficient alloresponses in four of six cases, whereas G-PBMC stimulated poorly in the remaining two cases. Also, in allo-MLC with irradiated G-PBMC we detected lower amounts of IFN-gamma (P = 0.04) and of IL-2 (P = 0.06) than in allo-MLC with preG-PBMC. Furthermore, freshly isolated preG-PBMC and G-PBMC from each donor exerted comparable allogeneic responses to HLA-incompatible irradiated mononuclear cells in all cases. However, G-PBMC showed no NK activity against K562 target cells at any effector:target ratio tested. These data suggest that normal G-PBMC may prevent Thl alloresponses, maintain efficient alloreactivity to HLA mismatched antigens and have impaired NK activity.

Circulating CLA+ lymphocytes from children with atopic dermatitis contain an increased percentage of cells bearing staphylococcal-related T-cell receptor variable segments.

Atopic dermatitis is an allergic T-cell mediated skin inflammation. Staphylococcus aureus colonization is very common in cutaneous atopic dermatitis lesions. The cutaneous lymphocyte-associated antigen (CLA) is a T cell skin homing receptor that defines T lymphocytes associated with the cutaneous immune response. To study whether CLA+ T cells from atopic dermatitis children present a selective expression for Staphylococcus aureus-related TCR Vbeta segments. Peripheral blood T cells were stained with HECA-452 (anti-CLA) and a panel of TCR Vbeta specific monoclonal antibodies and analysed by flow cytometry. Atopic dermatitis patients have a higher percentage of circulating CLA+ CD3+ lymphocytes compared with healthy controls. Patients with active atopic dermatitis during the study expressed a higher percentage of cells positive for the TCR Vbeta2 and Vbeta5.1 segments in the CLA+ but not in the CLA- subset. These TCR Vbetas are recognized by staphylococcal superantigens. Moreover, there was an increased percentage of HLA-DR+ expression by CLA+ Vbeta5.1+ T cells in patients with active atopic dermatitis, but those patients whose eczema was inactive had very similar values to healthy controls regarding TCR Vbeta and HLA-DR phenotype in circulating CLA+ T lymphocytes. Our data indicate that circulating skin-homing T cells of patients with active atopic dermatitis contain an increased percentage of cells bearing TCR Vbeta segments related with Staphylococcus aureus. Staphylococcus superantigens may therefore trigger expansion or at least circulation of appropriate CLA+ T cells.

Age-related changes in blood lymphocyte subsets of Saudi Arabian healthy children.

The age-related changes in absolute and percentage values of lymphocyte subsets in the peripheral blood of healthy children of different ages (1 month to 13 years) were studied by flow cytometry. The absolute and percentage values for most lymphocyte subpopulations differed substantially with age. Comparisons among age groups from infants through adults revealed progressive declines in the absolute numbers of leukocytes, total lymphocytes, and T, B, and natural killer (NK) cells. The percentages of T cells increased with age. Within the T-lymphocyte population, the CD8(+) subset increased but the CD4(+) subset decreased, resulting in a declining CD4(+)/CD8(+) ratio. The percentage of B cells declined, but that of NK cells remained unchanged. The percentage of HLA-DR+ T cells increased over time, but their number changed inconsistently. Our findings confirm and extend earlier reports on age-related changes in lymphocyte subpopulations. These data should be useful in the interpretation of disease-related changes, as well as therapy-dependent alterations, in lymphocyte subsets in children of different age groups.

Functional activity of immune cells in female MS-patients

Since the well documented immunological disturbances in patients suffering from multiple sclerosis are especially attributed to T-cells we felt it expedient to look also for the functional activity of lymphocytes, monocytes, granulocytes and natural killer cells in the peripheral blood of female MS-patients (n = 17) and healthy controls (n = 17). While MS-patients showed decreased levels of total lymphocytes, CD2(+)- and CD8(+)-cells the percentage of HLA-DR(+)-monocytes was increased, indicating a high activity level of these immune cells, whereas we could find no differences in the functional tests of monocytes, granulocytes and natural killer cells between MS-patients and healthy controls. The percentage of HLA-DR(+)-T-lymphocytes increased with the duration of the illness and support the stronger consideration of clinical staging.

Bronchoalveolar lavage cell findings in three types of eosinophilic pneumonia: acute, chronic and drug-induced eosinophilic pneumonia

There are clinically different types of eosinophilic pneumonia (EP) but no study to date has compared pulmonary inflammatory cells between different types of EP, such as acute eosinophilic pneumonia (AEP), chronic eosinophilic pneumonia (CEP) and drug-induced eosinophilic pneumonia (drug-EP). The present study compared bronchoalveolar lavage fluid (BALF) cell findings to elucidate whether the profiles of the pulmonary inflammatory cells were different among the three types of EP. Clinical records of 28 patients with EP, consisting of eight AEP patients, 10 CEP patients and 10 drug-EP patients, were examined retrospectively. The differential cell counts, the CD4+ CD8+ ratio of lymphocytes, the percentage of HLA-DR+ in CD4+ and CD8+ lymphocytes, and the mean number of nuclear segmentations in eosinophils in BALF were compared among the three types of EP. The numbers of total cells, lymphocytes, neutrophils and eosinophils in BALF from patients with AEP were increased compared with those from normal subjects, and patients with CEP and drug-EP. The CD4+ CD8+ ratio of the BALF lymphocytes in patients with AEP, which exceeded 1·0 in all patients, was significantly higher than that in normal subjects. The percentages of HLA-DR+ cells in CD8+ lymphocytes in BALF from patients with CEP were significantly higher than those from patients with AEP and drug-EP. There was no significant difference in the mean number of nuclear segmentations in eosinophils in BALF among the three types of EP. The BALF cell findings in patients with EP showed some characteristics in accordance with type of EP. It is suggested that pulmonary neutrophils and lymphocytes, rather than eosinophils, may be related to the pathogenesis of the different types of EP.

Changes in Antigen Expression on B Lymphocytesduring HIV Inf ection

Involvement of the B cell compartment during HIV infection plays an important role in the development of immune deficiency. The aim of this study was the identification of specific antigen expression changes on B lymphocytes in HIV infection as surrogate markers in this cell population of certain functional aspects that could be easily measured. We investigated the level of expression of a series of constitutive surface markers in B lymphocytes (HLA-DR, CD19, CD20, CD21, CD22) from 30 HIV-seropositive adult patients and 20 normal controls. By means of quantitative flow cytometry, we assessed the number of antigen molecules per cell using standard beads to convert fluorescence intensity into antibody-binding capacity (ABC). We correlated these results with disease stage and cellular markers of immune activation. The expression of CD20 was significantly increased when B cells from HIV-infected individuals were compared with those from uninfected subjects. No differences were found in the density expression of HLA-DR on activated CD3+ T cells between HIV+ and HIV– subjects. In contrast, B cells from HIV+ patients showed a significantly lower number of HLA-DR molecules per cell compared to normal controls. A significantly lower number of CD21 molecules per cell was also found on B lymphocytes from HIV+ patients compared to normal controls. No differences in CD19 and CD22 expression levels on B cells between HIV-infected patients and controls were detected. No differences between HIV disease stages were detected for CD19, HLA-DR, CD21 and CD22. In contrast, differences between stages were found for CD20 expression, which showed significant changes in individuals with less than 200 CD4 T cells/µl. The data presented here demonstrate that B lymphocytes of HIV-infected individuals exhibit specific changes in receptor density expression during HIV infection and that these changes are often correlated with progression of disease, as measured by CD4 counts. No correlations were found between the percentages of HLA-DR+ T cells and the ABC values of the B cell markers studied. These antigen expression modulations may contribute to the humoral abnormalities during HIV infection and to the development of severe, recurrent or multiple bacterial infections. Therefore, quantitative flow cytometry may be of value in HIV infection both for clinical and biological studies. The study of antigen density changes on B cells in HIV infection may allow a better understanding of the humoral immune defects observed in these patients and provide insights into the functional defects of B cell compartment in HIV-infected individuals.

Hereditary haemochromatosis as an immunological disease.

Hereditary haemochromatosis as an immunological disease.

Flow cytometry tear analysis in patients with chronic allergic conjunctivitis

Tears from patients with chronic allergic conjunctivitis were analyzed with flow cytometry to determine the function of the T lymphocyte-related immunological reactions in the disease pathogenesis. Twenty-eight patients and 22 normal volunteers were studied; tears were obtained with capillary tubes. T helper/T suppressor ratios and the percentages of HLA DR+, CD23+, and CD3+ cells were significantly higher in patients than in controls. This study provides support for the hypothesis that chronic allergic conjunctivitis results from T lymphocyte-related immunological reactions.

Characterization of T cells transmigrating through human endothelial cells in patients with HTLV-I-Associated myelopathy

We investigated the surface markers as well as the expression of β 2-integrin (LFA-1β/CD 18), in T cells migrating through human umbilical vein endothelial cells (EC) in patients with HTLV-Iassociated myelopathy (HAM). No significant differences were found in the percentages of both HLA-DR + T cells and total CD4 + cells and in the expression of β 2-integrin between the ECtransmigrated and the EC adherent T cells. However, the percentages of HLA-DR+CD4+ cells in the transmigrated cells were significantly higher than those in the adherent cells. These results suggest that activated or HLA-DR +CD4 + T cells play an important role as the first trigger in the immunopathogenesis of HAM.

Psychoimmunoendocrine aspects of panic disorder

AbstractStress‐responsive neurohormonal systems are involved in major depression (MD) and panic disorder (PD). The immune system, which is closely connected with neuronal and hormonal systems, has been studied in MD: a systemic immune activation has been recently reported. To determine whether similar changes in the immune function are present also in PD, we studied leukocyte enumeration by flow cytometry in conjunction with monoclonal antibody staining, in 18 PD, 23 MD in drug‐free conditions and 20 controls. We found a significantly higher percentage of HLADR + (p <0·001) and of CD 19 cells (p < 0·01) in PD and MD and a lower percentage of CD3 (p < 0·05) in PD. Urinary free cortisol levels were higher in MD compared to PD. A pattern of lymphocyte subpopulation distribution compatible with an activation of the immune system was found in MD and PD. This activation was present also with high glucocorticoid levels, suggesting a possible defect of glucocorticoid receptors.

Leukocytapheresis therapy, performed with leukocyte removal filter, for inflammatory bowel disease

Leukocytapheresis (LCAP), performed with a leukocyte removal filter, was administered five times, at 1-week intervals, for 5 weeks of intensive therapy and five times, at approximately 1-month intervals, for approximately 5 months of maintenance therapy, to 13 patients with inflammatory bowel disease (IBD) diagnosed as ulcerative colitis (UC) in 8 and Crohn's disease (CD) in 5. Clinical and blood examinations showed no side effects in any of the patients. During the intensive therapy, excellent or moderate clinical response was recognized in 11 of the 13 patients (84.6%), of whom 6 had a dramatic response; the excellent or moderate clinical response continued throughout the maintenance therapy in 8 of the patients (61.5%). Flow cytometry showed that the patients who had improved generally had high values for percentages of HLADR+, HLADR+CD3+, and HLADR+CD8+ cells before the first LCAP, and that these values and the C-reactive protein levels and erythrocyte sedimentation rates had decreased to the normal range by the end of both intensive and maintenance therapy. In the patients who showed poor response, in contrast, all the above values had been at or near normal before the initial LCAP administration. The clinical improvement in the absence of any additional medical treatment suggests that LCAP has the capacity to influence the causal mechanism(s) of IBD and that IBD is strongly associated with the cell-mediated immune response.

Immunologic analyses of peripheral leukocytes from workers at an ethical narcotics manufacturing facility.

Little information exists about possible adverse health effects associated with workplace exposure to opiate compounds. We have previously reported opiate-specific IgG antibodies, positive epicutaneous tests, and pulmonary function decrements in workers exposed occupationally to opiates. In the present work, we extended these findings to investigate the effect of occupational opiate exposure on lymphocyte subpopulations and mitogen-induced lymphoblastogenesis. Thirty-three opiate-exposed workers and 8 nonexposed control workers were evaluated for lymphocyte subpopulation absolute numbers and percentages, by evaluating cell surface antigen expression with flow cytometry. A complete blood count with differential, common clinical chemistry parameters, and serum immunoglobulin levels were also evaluated. Opiate-exposed workers showed significantly (p < .05) increased absolute numbers and percentages of HLA-DR+ cells (MHC class II histocompatibility antigen), significantly (p < .01) decreased percentages of T helper-inducer (CD4+) cells, and significantly (p < .05) decreased numbers of basophils, compared with nonexposed opiate workers from the same factory. A trend toward reduction in the T helper-inducer (CD4+)/T cytotoxic-suppressor (CD8+) lymphocyte ratio was also evident. There was also a significant decrease in lymphocyte activity stimulated by pokeweed mitogen (p < .05) in opiate-exposed workers. These data indicate that occupational opiate exposure may change the number and types of circulating peripheral blood leukocytes, or alternatively, alter the expression of receptors on the surface of these cells. In addition, occupational opiate exposure appears to decrease the sensitivity of B-cells to pokeweed mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

T cell subsets In peripheral blood and cerebrospinal fluid from children with aseptic meningitis

T cell subsets in peripheral blood (PB) and cerebrospinal fluid (CSF) obtained from patients with aseptic meningitis were studied using quantitative two-color fluorescence analysis with a flow cytometer. The percentage of HLA-DR+/CD3+ lymphocytes (activated T cells) in CSF was significantly increased in the recovery phase when compared to the acute phase, while no significant change in the activated T cells in PB was observed. More interestingly, CD4+ T lymphocytes in CSF were increased in the acute phase and subsequently decreased in the recovery phase. Instead, CD8+ T lymphocytes gradually accumulated into the CSF in the recovery phase, resulting in a successive decrease in the CD4/CD8 ratio. On the other hand, the CD4/CD8 ratio in PB remained normal during the course of aseptic meningitis. The present results suggest that T lymphocytes (CD4+ subset in the acute phase and CD8+ in the recovery phase) could be infiltrated and further activated at the site of inflammation, possibly in the subarachnoid space in the patients with aseptic meningitis.

Natural killer cell activity in major depression: Relation to circulating natural killer cells, cellular indices of the immune response, and depressive phenomenology

Maes, Michael, Herbert Y. Meltzer, Wim Stevens, Joseph Calabrese and Paul Cosyns: Natural Killer Cell Activity: Relation to Circulating Natural Killer Cells, Cellular Indices of the Immune Response and Depressive Phenomenology. Prog. Neuro-Psychopharmacol. & Biol. Psychiat. 1994, 18 :3 717–730. 1. Recently, blunted natural killer cell activity (NKCA) has been found in major depression. The present study investigates the relationships between ex vivo blunted NKCA in major depression, number or percentage of NKC, in vivo indices of systemic immune activation and depressive phenomenology. 2. Toward this end, NKCA, absolute number of leukocytes and number or percentage of lymphocytes, monocytes, neutrophils, activated T lymphocytes (HLA-DR +, CD25 +) and NKC (CD3 −CD56 +) were determined in 13 normal controls and 36 depressed inpatients. 3. NKCA was significantly and positively related to number and percentage of NKC in the peripheral blood. The major depression-related reduction in NKCA was not related to alterations in peripheral NKC. There were significant negative correlations between NKCA and number or percentage of leukocytes, monocytes, neutrophils and HLA-DR + T cells. Up to 50% of the variance in NKCA could be explained by the regression on the number of monocytes, percentage of HLA-DR + T and NKC cells, and diagnostic classification. Up to 43% of the variance in NKCA was explained by depressed mood, somatic anxiety and less diurnal variation. 4. The results show that blunted NKCA in major depression is not related to alterations in peripheral NKC, but reflects in part the systemic immune activation in that illness.

Changes in populations of HLA-DR+CD3+ cells and CD57-CD16+ cells in alopecia areata after corticosteroid therapy.

We investigated the populations of activated T (HLA-DR+CD3+) cells and natural killer (CD57-CD16+) cells in the peripheral blood of patients with various types of alopecia areata (AA) and noted any changes that occurred in the said populations after administration of local and systemic corticosteroid therapy. In type 2 (severe multiple AA and alopecia totalis) and type 3 (alopecia universalis), the mean percentages of HLA-DR+CD3+ cells and CD57-CD16+ cells were significantly higher when compared with those of the normal controls. The percentages of both subsets in type 1 (mild AA) and the normal controls were consistent. Twenty-four patients in types 2 and 3 had received corticosteroid treatment, and all patients experienced new hair growth. With the changes in disease activity, the populations of HLA-DR+CD3+ cells in these patients after corticosteroid therapy significantly decreased when compared with those recorded prior to treatment. Subsequent to treatment, the mean percentages of CD57-CD16+ cells decreased to levels that were not significant relative to that of the normal controls. These findings indicate that HLA-DR+CD3+ and CD57-CD16+ cells in the peripheral blood of patients with AA may be correlated with the disease activity of AA.

Lymphocyte subpopulations analysis in peripheral blood in polymyalgia rheumatica/giant cell arteritis.

The phenotypic characteristics of peripheral blood lymphocytes were investigated in 22 patients suffering from active polymyalgia rheumatica/giant cell arteritis (PMR/GCA) prior to steroid treatment. We observed a significant reduction in the absolute number and the relative percentage of CD4-, CD8+ and CD3+, CD16+ and/or CD56+ cells compared to controls. Fifteen patients were investigated prospectively over a 6-month period of prednisone therapy. At the end of the study CD4-CD8+ cells had increased significantly compared to baselines, CD3+ CD16+ and/or CD56+ cells remained significantly lower when compared to controls. We did not observe any abnormalities in the absolute number and percentage of HLA-DR+ T lymphocytes, CD5+ B cells and NK cell phenotypes before or during steroid treatment. Our study confirms that there was significant increase in the absolute number of CD8+ T cells during steroid treatment in the PMR/GCA patients, but indicates the persistence of an immunological alteration despite the control of disease manifestations.

Distinctive increases in HLA-DR+ and CD8+57+ lymphocyte subsets in Wegener's granulomatosis.

Lymphocyte subset abnormalities have been observed in a series of patients diagnosed with Wegener's granulomatosis (WG). Fifteen patients with WG were evaluated for lymphocyte subset abnormalities by two-color immunofluorescence flow cytometry. The WG group showed a decrease in CD4+ cells and an extraordinary increase in HLA-DR+ cells. The average percentages of HLA-DR+ cells of the normal group and WG group were 11.0 +/- 4.0 and 40.5 +/- 13.9% (CD3+HLA-DR+ = 20.3 + 9.4%). Within the CD8 family, CD8+57+, CD8+38+ and CD8+HLA-DR+ cells were markedly elevated. Our findings differ from other series which reported that the lymphocyte subsets in the peripheral blood of patients with WG were normal.

Psychological factors, immunologic activation, and disease activity in rheumatoid arthritis.

The purpose of this study was to use structural equation modeling techniques to examine potential interrelationships among psychological factors, immunologic activation, and disease activity in rheumatoid arthritis (RA). The subjects were 80 male patients with a diagnosis of classic or definite RA. Measures included the Beck Depression Inventory, the Arthritis Helplessness Index, and the Arthritis Impact Measurement Scales (AIMS) pain score. Joint counts and immunophenotypic analyses of peripheral blood lymphocytes also were collected. Path analysis showed that percentage of HLA-DR+ cells in the peripheral blood and helplessness were related to join count. In addition, joint count had an effect upon depression. Depression had an effect upon pain, but there was no reciprocal effect of pain upon depression. This study describes a preliminary path model of interrelationships among psychological factors, immunologic activation, and disease activity in RA.

Circulating Activated T Lymphocytes in Autoeczematization

Autoeczematization, the symmetric diffuse spread of a previously localized dermatitis, has an unclear etiology although some investigators have postulated that activated T lymphocytes play a role. Two estimates of activation of peripheral T lymphocytes are the cell surface expression of the HLA-DR antigen and the interleukin 2 receptor (IL-2R). We measured the percentage of circulating activated T lymphocytes in nine patients with autoeczematization compared with normal controls (n = 10), patients with stasis dermatitis (n = 6), and patients with severe (n = 10) or mild (n = 8) psoriasis. The percentage of activated T lymphocytes was determined by fluorescent, activated cell sorter analysis of peripheral leukocytes doubly stained with antibodies to T lymphocytes and HLA-DR antigen or IL-2R. Statistically significant elevations of HLA-DR- and IL-2R--positive T lymphocytes were seen in autoeczematization patients (P less than .004 and P less than .04, respectively) and those with severe psoriasis (P less than .004 for HLA-DR antigen and IL-2R). Percentages of HLA-DR- and IL-2R--positive T lymphocytes in patients with mild psoriasis were not significantly elevated. Two patients with autoeczematization had a reduction of their previously elevated levels of HLA-DR- and IL-2R--positive T lymphocytes after treatment. These data suggest a possible role for circulating activated T lymphocytes in the pathogenesis of autoeczematization and possibly in severe psoriasis.