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Lymphocyte subsets and viral load in male AIDS patients with major depression: naturalistic study.

This study investigated the relationships between lymphocyte subsets and viral load in AIDS patients with and without major depression. During a 7-year period, a total of 60 male hospitalized AIDS patients were recruited in this study. The diagnosis of major depression in patients was made by the same psychiatrist according to the 4th edition of the Diagnostic and Statistical Manual for Mental Disorders criteria. All patients had data for CD4, CD8 and CD4/CD8, and only 42 patients had viral load data. Of 60 AIDS patients, 32 patients had received highly active antiretroviral therapy and received subsequent assessment of lymphocyte cell counts 1 month later. Using ancova with age adjustment, the authors found that patients with major depression (n = 22) had significantly lower CD8 cell counts than patients without major depression (n = 38). However, CD4 cell counts and CD4/CD8 ratios were not significantly different between these two groups. In addition, there was no significant difference in viral load between patients with major depression (n = 16) and patients without major depression (n = 26). Of 32 patients received highly active antiretroviral therapy, 14 patients with an antidepressant (e.g. fluoxetine 20 mg/day) had significantly decreased CD4 and not CD8 cell counts and significantly reduced CD4/CD8 ratios during a period of 1 month. In conclusion, these results suggest that AIDS patients with major depression had significantly lower CD8 cell counts and might have a more severe inflammation/immunity reaction than patients without major depression.

Acquired Immunodeficiency Syndrome↗

Phenotypic changes in a CD4+ lymphocyte subset correlate with a conversion from suppressor to helper inducer function.

The monoclonal antibodies WR16 (CD45RA) and WR19 were used to isolate two reciprocal subsets of CD4 lymphocytes by negative selection. The CD4+/WR16-/WR19+ subset exhibited helper-inducer activity in a pokeweed mitogen (PWM)-driven Ig secretion assay, whereas the CD4+/WR16+/WR19- subset showed suppressor activity. When the CD4+/WR16+/WR19- subset was cultured in phytohaemagglutinin (PHA) or purified protein derivative (PPD) there was increased expression of the antigen binding WR19 but the cells remained WR16 negative. Cultures of CD4+/WR16+/WR19- lymphocytes with PHA or PPD induced a phenotypic change that resulted in a population which was CD4+/WR16-/WR19+. Investigation of the functional activity of the CD4+/WR16+/WR19- subset, before and after activation and phenotypic change to WR16-/WR19+, indicated that the change in phenotype correlated with a functional conversion from suppressor to helper-inducer activity. These results suggest that the CD4+/WR16+/WR19- suppressor subset comprises cells that differentiate to WR16-/WR19+ helper-inducer cells after exposure to antigen or mitogen.

CD4 Antigens↗

Analysis of leucocytes and lymphocyte subsets for different clinical stages of naturally acquired feline immunodeficiency virus infection.

We report alterations in leucocytes numbers and lymphocyte subset percentages, determined by flow cytometry, for three observed and previously defined clinical stages (asymptomatic carrier (AC), AIDS-related complex (ARC) and AIDS) of naturally occurring FIV infection. Unstaged FIV-positive cats had significantly lower numbers of total leucocytes (WCC) and neutrophils, lower percentages of PanT+ and CD4+, lower CD4:CD8 ratio and a higher percentage of B cells compared with unstaged FIV-negative cats. When FIV-positive cats were separated into clinical stages and compared with matched FIV-negative cats, AC FIV-positive cats had a significantly lower WCC, lower absolute numbers of neutrophils and lymphocytes, lower percentages of CD4+ and CD8+ cells, lower CD4:CD8 ratios and a higher percentage of B cells than healthy FIV-negative cats. ARC FIV-positive cats had lower percentages of PanT+ and CD4+ cells, lower CD4:CD8 ratios and higher percentages of B cells than matched FIV-negative cats. FIV-positive cats with AIDS had significantly lower percentages of CD4+ cells than matched FIV-negative cats. Comparisons among the three observed clinical stages of FIV-positive cats showed that AC FIV-positive cats had significantly lower WCC, significantly lower absolute numbers of neutrophils and a significantly lower percentage of CD8+ cells than ARC FIV-positive cats. AIDS FIV-positive cats had a significantly lower percentage of B cells than AC or ARC FIV-positive cats. FIV-positive cats had a similar leucocyte response to illness as FIV-negative cats but had consistently lower percentages of CD4+ lymphocytes. Thus, in the staging of FIV, a rise in the percentage of CD8+ lymphocytes could be used to distinguish between AC and ARC and a fall in the percentage of B lymphocytes could distinguish AIDS from AC and ARC.

Animals↗

HLA-DR typing and lymphocyte subset evaluation in rheumatic heart disease: a search for immune response factors.

Several autoimmune diseases have been associated with increased frequencies of specific histocompatibility (HLA) antigens, particularly for the D (DR) locus, that may be linked to immune response genes. Rheumatic valvular heart disease (RHD) has been postulated to have autoimmune features, but HLA associations have not been established. We, therefore, performed HLA-DR typing in 33 consecutive patients with RHD and in 82 normal blood bank control subjects. We also evaluated the frequencies of lymphocyte subsets by means of monoclonal antibodies and immunofluorescence flow cytometry and made functional correlations for the natural killer cell (NKC) in patient subsets. The DR patterns in RHD were heterogeneous. However, significant differences were noted for DR4 and DR6. DR4 was present in 52% (17 of 33) of RHD patients vs 32% (26 of 82) of control subjects (p less than 0.05). DR6 was present in 6% (2 of 33) of patients vs 26% (21 of 82) of control subjects (p less than 0.02). The associated relative odds of DR4 was 2.3 and the etiologic fraction was 0.30. The relative odds of DR6 was 0.19 and the preventive fraction was 0.21. A distinct clinical profile was not associated with DR4 positivity or DR6 negativity. The frequency of lymphocyte subsets was not significantly changed except for OKT8. Median NKC numbers tended to be higher in RHD patients than in control subjects (p less than 0.05). In contrast, NKC functional activity tended to be lower in RHD; median lymphocyte to target cell (K562 line) ratio resulting in 50% killing (L/T 50) was 20.5 in RHD patients vs 11.5 in control subjects (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Lymphocyte subset analysis for the diagnosis of rejection and infection in recipients of liver transplants.

We retrospectively investigated the predictive value of lymphocyte subset changes in the peripheral blood of 37 consecutive liver transplant recipients for rejection and infection, both bacterial and cytomegalovirus, during a period of 2 years. Total lymphocyte count correlated with biopsy-proven rejection. There was moderate elevation of CD16+ count during the course of bacterial infection.

Bacterial Infections↗

Circadian rhythm of T-lymphocyte subsets, cortisol and cyclosporin in kidney-transplanted subjects.

The present study deals with the 24-h changes in circulating lymphocyte subpopulations in eight subjects with kidney grafts established for 2 to 5 years and treated with cyclosporin. The control group consisted of ten age-matched clinically healthy subjects. The chronobiological analysis of time series documented that the circadian rhythm of T-lymphocyte subsets is undetectable in transplanted subjects. Cortisol rhythmicity persists, however, suggesting that the abolition of T-cell rhythmicity is not attributable to a desynchronisation of the adrenal cycle. Even though the therapy was combined with prednisolone, the abrogation of rhythmicity for T-lymphocyte subpopulations seems to be related to the immunosuppressive action of cyclosporin, as the plasma concentrations of the drug show no periodic variations along the 24-h span. Antirejection therapy of kidney-transplanted subjects could be adjusted so that cyclosporin is given at a time that would promote suppression of T-lymphocytes without altering their rhythmic performance.

Adult↗

Changes in lymphocyte subsets in human immunodeficiency virus-positive persons with < 5 CD4 T lymphocytes/mm3.

All patients seen at the Royal Free Hospital, London, who had at least one CD4 T lymphocyte count of < 5 cells/mm3 (n = 166) were prospectively followed to assess changes in their total T lymphocyte and CD8 T lymphocyte counts over time. While overall there were no clear trends towards a drop or increase in either count, persons who died during the study experienced a rapid drop in both CD8 T lymphocyte and total T lymphocyte levels in the months preceding death. Multivariate Cox proportional hazards models revealed that both the total T lymphocyte count and CD8 T lymphocyte count provided important prognostic information for survival. Despite almost a complete absence of CD4 T lymphocytes, lymphocyte subset monitoring is useful in identifying decreasing CD8 T lymphocyte levels that predict short-term prognosis.

CD4-Positive T-Lymphocytes↗

Distribution of B lymphocyte subsets in normal lymphoid tissue.

Using the ABC avidin-biotin peroxidase techniques and a series of monoclonal antibodies against B cell associated antigens, the anatomical distribution of B lymphocyte subsets was studied in reactive lymph node, tonsil and spleen. Evidence is presented for at least five major phenotypically distinct B cell subsets, each localized to specific compartments of peripheral lymphoid tissue. The possible relationship of these subsets of B lymphocytes to activation, maturation and function in the B cell lineage is discussed.

Antibodies, Monoclonal↗

Quantification of lymphocyte subsets based on positive immunomagnetic selection of cells directly from blood.

Lymphocyte subset quantification can be performed directly in unseparated anticoagulated blood by means of immunomagnetic (IM) particles. The method is fast and reliable and so simple as to be employable in small laboratories. This article reviews the method in detail and describes the results obtained with the IM quantification method in some clinical situations.

B-Lymphocytes↗

Changes in lymphocyte subsets in children with newly diagnosed type 1 diabetes mellitus.

UNLABELLED: The aim of this study was to assess changes in selected peripheral blood lymphocyte subsets in children and adolescents with newly diagnosed type 1 diabetes mellitus (DM) and determine the correlation between these changes and other immunological markers. The study involved a group of 39 patients aged 2-14 years and a control group. The number of T- and B-lymphocytes and the number of CD4, CD8, CD4/HLA-DR, CD8/HLA-DR, CD5/CD20 subsets were measured by flow-cytometry using monoclonal antibodies. Islet cell antibodies (ICA) and antibodies to glutamic acid decarboxylase (GADA) were assessed. In both the diabetic and control groups the number of T-and B-lymphocytes were within normal limits. In patients with DM, the percentage of CD5+/CD20+ cells was significantly increased compared with the control group (p < 0.0001). ICA were positive in 80% of patients and GADA in nearly 65%. A positive correlation between the CD5/CD20 subset and ICA and GADA was found. In patients with a high percentage of CD5+/CD20+ lymphocytes, a higher percentage of activated subsets (CD4/HLA DR and CD8/ HLA DR) was detected. IN CONCLUSION: CD5/ CD20 lymphocyte subsets are a good additional marker of autoimmunological processes in DM.

Antigens, CD19↗

Expression of interleukin-2 receptor and HLA-DR on lymphocyte subsets of gingival crevicular fluid in patients with periodontitis.

Expression of interleukin-2 receptor (IL2R) and HLA-DR on lymphocytes of gingival crevicular fluid (GCF) was examined by two-color flow cytometric analysis. GCF from 15 patients with periodontitis was collected by crevicular washing. Mononuclear cells were isolated by Ficoll-paque gradient centrifugation from inflamed gingival tissue (GT) and peripheral blood (PB) sampled from each of the 15 patients. Lymphocyte subsets were detected by using monoclonal antibodies (mAb) of Leu 12 (CD19), Leu 4 (CD3), Leu 3a (CD4) and Leu 2a (CD8) directed to B cells, T cells, helper/inducer T cells (Th) and suppressor/cytotoxic T cells (Ts), respectively. Anti-IL2R (CD25) and anti-HLA-DR were used as lymphocyte activation markers. IL2R- or HLA-DR-positive fractions in Th, Ts and B cells were calculated. Percentage of IL2R-positive fraction in Th (IL2R+ Th) of GCF (34.0%) was significantly higher than those of GT (18.4%) and PB (13.7%). IL2R-positive fraction in B cells (IL2R+ B) of GCF was the highest among the three groups (23.9% in GCF, 12.5% in GT, 6.3% in PB). Ts did not express IL2R regardless of the origin of the samples. Compared with PB and GT, GCF showed significantly higher HLA-DR expression on Th and Ts in GCF (PB: 8.7% and 27.1%; GT: 27.9% and 50.3%; GCF: 44.7% and 65.3%). These results suggest that lymphocytes in GCF were highly activated and are related to the local host immune response in periodontitis.

CD4-CD8 Ratio↗

T lymphocyte subset abnormalities and HLA antigens in scleroderma (systemic sclerosis).

Studies of T lymphocyte subsets were carried out in a group of 50 scleroderma patients, of whom 46 were also HLA phenotyped. The total lymphocyte count was depressed in 22 patients, and CD4 (helper cells) numbers were normal. CD8 (suppressor-cytotoxic) cells were reduced in 27 patients, and the CD4/CD8 number ratio increased above normal in three additional patients, resulting in 30 patients being classified as CD8-deficient. In the 46 patients HLA phenotyped, DRw8 was significantly increased in the entire patient group, but when the patients were subdivided into CD8-deficient (n = 29) and CD8-normal (n = 17), the increase in DRw8 was confined to the CD8-deficient patients. B18 was also increased in patients with limited sclerosis, while DR4 and DRw53 were significantly decreased and DR5 significantly increased in patients with more extensive skin sclerosis. These findings suggest that scleroderma is a heterogeneous condition and that this heterogeneity is reflected in different HLA profiles in patients subtyped according to their clinical profile and subpopulations of T cells.

Adult↗

Effects of radiation on survival and recovery of T lymphocyte subsets in C3H/HeN mice.

The aims of this study were to determine the radiosensitivities of murine thymic and splenic CD4+ and CD8+ lymphocytes and to evaluate the regeneration of these cells in a model of radiation-induced hematopoietic and immune suppression. CD4+ and CD8+ cells were quantitated using two-color flow-cytometric analysis. Cells obtained from C3H/HeN mice 24 hours after exposure to 0.25-8.0 Gy (0.4 Gy/min) 60Co were used to determine D0 values. Thymic CD4+ cells contained a radiosensitive subpopulation with a D0 of 0.97 +/- 0.05 Gy and a radioresistant subpopulation that survived exposures up to 8.0 Gy. CD8+ cells also contained a radiosensitive subpopulation with a D0 of 1.24 +/- 0.05 Gy and a radioresistant subpopulation with a D0 of 3.93 +/- 2.01 Gy. Double-positive thymic CD4+/CD8+ cells were uniformly radiosensitive, with a D0 of 1.03 +/- 0.28 Gy. Multiple T lymphocyte subpopulations based on radiosensitivity and CD4/CD8 antigen expression were also observed in the spleen. When mice were exposed to a sublethal 6.5-Gy radiation dose and recovery of T lymphocyte subsets was monitored, the relative radioresistance of CD4+ cells resulted in a selective enrichment of these cells among the surviving thymocytes and splenic lymphocytes. This relative enrichment of CD4+ cells became even more prominent 7 days after irradiation, when atrophy of the organs was greatest. Similar, although less dramatic, effects were observed for CD8+ cells. These studies demonstrate that (1) multiple T lymphocyte subpopulations can be identified based on radiosensitivity and CD4/CD8 antigen expression; (2) both CD4+ and CD8+ cells contain radioresistant subpopulations, with the CD4+ subpopulation being more resistant than the CD8+ subpopulation; and (3) although the number of radioresistant CD4+ cells is quite small, they persist in increased proportions during the periods preceding and corresponding to postirradiation hematopoietic recovery.

Animals↗

Lymphocyte subsets in hemodialysis patients treated with recombinant human erythropoietin.

We investigated whether recombinant human erythropoietin (rhEPO) therapy affected the lymphocyte subsets in patients on long-term maintenance hemodialysis (HD) with severe anemia. Before treatment, the numbers of peripheral blood lymphocyte, CD3+, CD4+, CD8+, and CD20+ cells were decreased in HD patients compared to those in healthy subjects, while the number of CD3+HLA-DR+ cells was increased in HD patients compared to that in healthy subjects. Furthermore, the number of CD4+CD45RA+ (naive T) cells was markedly decreased in HD patients (112 +/- 77 vs 241 +/- 146/microliters; P < 0.01). The number of CD8+S6F1+ (cytotoxic T) cells in HD patients was also less than that in healthy subjects (247 +/- 104 vs 122 +/- 83/microliters; NS). During a 6-month period of rhEPO therapy, we found that the low level of CD4+CD45RA+ cells gradually increased (from 112 +/- 18 to 163 +/- 24/microliters; P < 0.01) with the elevation of hematocrit values (from 21.5 +/- 1.7 to 28.2 +/- 3.5%; P < 0.05). The number of CD3+HLA-DR+ cells decreased after 1 month of rhEPO therapy (from 93 +/- 14 to 46 +/- 13/microliters) and gradually declined throughout the 6-month study period. In our in vitro study, we demonstrated that no effects were observed on [3H]thymidine uptake in the T cell subsets at various concentrations of rhEPO. These results suggest that rhEPO-induced immunoregulation is mediated by an indirect stimulatory effect on the immune system, this stimulation being accompanied by an improvement in physical condition.

Adult↗

Lymphocyte subsets identified by monoclonal antibodies in healthy children.

The distributions of lymphocyte subsets and monocytes in the peripheral blood mononuclear leukocytes of 72 normal children from 2 months to 13 5/12 yr were examined using quantitative immunofluorescence analysis with monoclonal antibodies. Distinct decreases with age were found in the total leukocyte counts, the percentages and the absolute numbers of peripheral blood mononuclear leukocytes. The percentages of Leu-2a+ cells, Leu-7+ cells, and Leu-M3+ cells significantly increased with age, whereas the percentages of Leu-3a+ cells, Leu-4+ cells, and 2H7+ cells significantly decreased with age. As a result, ratios of Leu-3a+/Leu-2a+ decreased with age. No prominent differences with age were found in the proportions of Leu-10+ cells and HLA-DR+ cells.

Adolescent↗

The sequential analysis of T lymphocyte subsets and interleukin-6 in polymyalgia rheumatica patients as predictors of disease remission and steroid withdrawal.

CD4 and CD8 T lymphocyte subsets, the late T cell activation marker, HLA-DR, and serum interleukin-6 (IL-6) levels of 57 polymyalgia rheumatica (PMR) patients were followed over 2 yr to investigate whether they could be used to predict the safe withdrawal of steroid therapy. Cell phenotypes were studied by flow cytometry and IL-6 levels by ELISA. %CD8 cells were reduced below the normal range in PMR patients prior to steroid therapy. In 56% of patients, the %CD8 T lymphocytes failed to return to normal levels when quiescent disease allowed cessation of steroid therapy. Activated CD8 T cells, as detected by HLA-DR positivity, were above the normal range at the initiation of therapy and showed a negative correlation with %CD8 T cells. The serum concentration of IL-6 fluctuated over 24 months, and the correlation between IL-6 and erythrocyte sedimentation rate (ESR) seen prior to treatment was not seen at later intervals. The %CD8 T cell and serum IL-6 levels are not a good indicator of disease activity in PMR and are, therefore, unable to predict the safe withdrawal of steroids.

Administration, Oral↗

Determination of T-lymphocyte subsets on site in rural Tanzania: results in HIV-1 infected and non-infected individuals.

With the FACSCount flow cytometer, counts of CD4, CD8 and CD3 lymphocytes and CD4/CD8 ratios were performed in a rural hospital in Tanzania. A total of 168 subjects (21 HIV-1 seropositive and 147 HIV-1 seronegative) were tested as part of a population-based serosurvey and AIDS education programme; 134 other subjects were hospitalized patients who had signs and symptoms suggestive of AIDS (69 HIV-1 seropositive and 65 HIV-seronegative). Mean values for the 147 HIV-1 seronegative subjects from the local population were 980 CD4 cells (95% CI 930, 1031), 598 CD8 cells (560, 635) and CD4/CD8 ratio 1.78 (1.68, 1.89). Seropositive subjects from the local population had significantly lower CD4 cell counts, higher CD8 counts and a lower CD4/CD8 ratio. CD4 cells were significantly lower and CD8 cells significantly higher in HIV-1 seropositive hospital patients compared to HIV-1 seronegative patients. However, 23 (35%) seronegative hospital patients had CD4 counts lower than 600. These results establish baseline values for the lymphocyte subsets in this population and indicate that this technique can be used in remote areas to monitor progress of HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗

[Changes in circulating lymphocyte subsets in alcoholic hepatopathies. Respective role of alcohol, hepatocellular insufficiency and malnutrition].

Peripheral lymphocyte subpopulations have been quantified by a direct and indirect, immunofluorescence technique, using monoclonal antibodies, in 22 patients with continued heavy drinking, hepatocellular dysfunction (spider angiomata, ascites, and factor V decrease) (group I), in 16 patients with a history of heavy drinking and abstinence maintained for at least 6 months and hepatocellular dysfunction (group II) and in 28 patients admitted for continued heavy drinking, without hepatocellular dysfunction (group III). Sixteen normal subjects were studied as controls. The total number of lymphocytes and T lymphocytes (OKT3+) were significantly reduced (p less than 0.001) in groups I and II. A significant decrease of B lymphocytes was observed in group II (p less than 0.02). The OKT8+ lymphocytes were significantly reduced in group I (p less than 0.01) and in group II (p less than 0.001); the decrease of the OKT4+ lymphocytes was significant in group II (p less than 0.01) only. The OKT4/OKT8 ratio was higher in group I (p less than 0.05) and group II (p less than 0.01) than in the control group. Normal values of total lymphocytes, B lymphocytes, T lymphocytes subsets and OKT4/OKT8 ratio were observed in group III. In group III, the lymphocyte subpopulations and OKT4/OKT8 ratio were similar in patients with or without abnormalities of liver function tests. In group I and II, no correlation was found between the lymphocyte subpopulations or the OKT4/OKT8 ratio and factor V or nutritional status assessed by anthropometrical and biological tests. T-cell imbalance in alcoholic liver disease does not seem to be related to alcohol consumption, factor V decrease or malnutrition.

Adult↗