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PubMed1997

Aging and lymphocyte subsets in the spleen and peripheral blood of the Sprague-Dawley rat.

This study was undertaken to determine the effects of aging on lymphocyte subsets in the peripheral blood and spleens of Sprague-Dawley rats. Rats aged 3,13 and 26 months were used in the study. Analyses of dual labeled lymphocytes from the 26 month animals show decreases in the numbers of lymphocytes due to decreased cellularity (spleen) or reduced lymphocyte percentages within the total white blood cell population (peripheral blood). In the spleens and blood of the oldest rats, there were reduced numbers of Total T, T helper/amplifier (Th/a), virgin Th and natural killer (NK) cells. Other changes were observed in the spleen but not peripheral blood. The numbers of T cytotoxic/suppressor cells (Tc/s) B cells, "autoimmune" B cells and NK cells were reduced in the spleen but remained within normal limits in peripheral blood. The data show aging exerts different effects on the peripheral blood and splenic compartments of the immune system. These differences may have teleological significance in relation to immune responses to xenobiotics and neoplastic cells.

Aging↗
PubMed2006

Characterization of lymphocyte subsets over a 24-hour period in Pineal-Associated Lymphoid Tissue (PALT) in the chicken.

BACKGROUND: Homeostatic trafficking of lymphocytes in the brain has important relevance to the understanding of CNS disease processes. The pineal gland of the chicken contains large accumulations of lymphocytes that suggest an important role related to homeostatic circadian neuro-immune interactions. The purpose of this initial study was to characterize the lymphocyte subsets in the pineal gland and quantitate the distribution and frequency of lymphocyte phenotypes at two time points over the 24-hour light:dark cycle. RESULTS: PALT comprised approximately 10% of the total pineal area. Image analysis of immunocytochemically stained sections showed that the majority of lymphocytes were CD3+ (80%) with the remaining 20% comprising B-cells and monocytes (Bu-1+), which tended to distribute along the periphery of the PALT. T-cell subsets in PALT included CD4+ (75-80%), CD8+ (20-25%), TCRalphabeta/Vbeta1+ (60%), and TCRgammadelta+ (15%). All of the T-cell phenotypes were commonly found within the interfollicular septa and follicles of the pineal gland. However, the ratios of CD8+/CD4+ and TCRgammadelta+/TCRalphabeta/Vbeta1+ within the pineal tissue were each 1:1, in contrast to the PALT where the ratios of CD8+/CD4+ and TCRgammadelta+/TCRalphabeta/Vbeta1+ each approximated 1:4. Bu-1+ cells were only rarely seen in the pineal interstitial spaces, but ramified Bu-1+ microglia/macrophages were common in the pineal follicles. Effects of the 24-h light:dark cycle on these lymphocyte-pineal interactions were suggested by an increase in the area of PALT, a decline in the density of TCRalphabeta/Vbeta1+ cells, and a decline in the area density of Bu-1+ microglia at the light:dark interphase (1900 h) compared to the dark:light interphase (0700 h). CONCLUSION: The degree of lymphocyte infiltration in the pineal suggests novel mechanisms of neuro-immune interactions in this part of the brain. Our results further suggest that these interactions have a temporal component related to the 24-hour light:dark cycle and that CD8+ and TCRgammadelta+ T-cells are preferentially recruited to the pineal follicles. Pineal microglia/macrophages were common and represent an important candidate for mediating these lymphocyte-pineal interactions via secretion of cytokines and chemokines.

Animals↗
PubMed1992

Changes of lymphocyte subsets after local irradiation for early stage breast cancer and seminoma testis: long-term increase of activated (HLA-DR+) T cells and decrease of "naive" (CD4-CD45R) T lymphocytes.

Blood lymphocyte subsets of early breast cancer patients and of men with stage I seminoma of the testis were studied up to 6 years after radiotherapy. Similar results were obtained in the two patient groups. After a temporary decrease, the CD4-w29 or "memory" T cells recovered completely, while the CD4-45R or "naive" T cells remained decreased up to 6 years after irradiation. The number of CD8 T lymphocytes did not change during or after treatment. Because of the decrease of a subset of CD4 cells, and the unchanged values of CD8 cells, the CD4/CD8 ratio decreased significantly after irradiation, and remained lower than before treatment up to 5-6 years after radiotherapy. The number of both HLA-DR positive CD4 and HLA-DR positive CD8 T cells ("activated" T cells) increased significantly after irradiation. The natural killer (NK) cells were not affected by treatment. We propose that the recovery of the CD4 cells is limited to the CD4-w29 ("memory") population because of thymic dysfunction in older humans. The impact of the observed immune modulation on the low susceptibility for infections after local irradiation, and on putative antitumour immune responses is discussed.

Adult↗
PubMed1993

Intrathyroidal lymphocyte subsets, including unusual CD4+ CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells, in autoimmune thyroid disease.

Intrathyroidal lymphocyte subsets were analysed in 13 euthyroid patients with autoimmune thyroid disease by two-colour flow cytometry and compared with subsets in peripheral blood. In both Graves' and Hashimoto's diseases, proportions of intrathyroidal CD5- B cells were higher than in peripheral blood. The numbers of such cells were correlated with serum levels of anti-thyroid microsomal antibodies. Proportions of T cells bearing alpha beta chains of T cell receptors (TCR alpha beta+ T; T alpha beta) and CD16+CD57+ natural killer (NK) cells were lower in the thyroid, but proportions of CD3hiTCR alpha beta-TCR gamma delta+ (T gamma delta) cells were not different. Proportions of CD4+Leu-8- helper T cells and CD4+CD57+ germinal centre T cells were higher and proportions of CD4+Leu-8+ suppressor-inducer T cells and CD8+CD57+ or CD8+CD11b+ suppressor T cells were lower than in the blood in both diseases. Proportions of CD5+ B cells were high in Graves' disease, and proportions of CD8+CD11b- cytotoxic T cells were high in Hashimoto's disease. Unexpectedly, CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells were present in thyroid tissues of both diseases. These findings suggest that: (i) an imbalance in the numbers of regulatory T cells and of NK cells that had appeared in the thyroid resulted in the proliferation of CD5- B cells, which were related to thyroid autoantibody production; (ii) CD5+ B cells and cytotoxic T cells are important for the different pathological features in Graves' and Hashimoto's diseases, respectively; and (iii) intrathyroidal CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells may be related to the pathogenesis of autoimmune thyroid disease.

Adolescent↗
PubMed1999

Quantitation of T lymphocyte subsets helps to distinguish dengue hemorrhagic fever from classic dengue fever during the acute febrile stage.

Activation of immunoregulatory T lymphocyte subsets has been observed in dengue viral infection, being more evident in dengue hemorrhagic fever (DHF) than in classical dengue fever (DF). There are, however, as yet no well-defined host markers to determine which patients with dengue viral infection will develop severe complications during the acute febrile stage of the disease. A study was performed to compare the cellular immune status in DHF, DF and non-dengue viral infections (NDF) in order to determine the value of these parameters in distinguishing DHF from classic DF and other viral infections during the acute febrile stage of the disease. This study involved 109 febrile patients admitted because of suspected DHF. Fifty patients were serologically confirmed cases of dengue infection, of which 25 had grade 1 or 2 DHF. There was a reduction in total T (CD3), CD4 and CD8 cells in DHF and demonstrated that a low level of CD3, CD4, CD8 and CD5 cells discriminated DHF from DF patients during the febrile stage of the illness. In contrast, B (CD19) cells and natural killer (NK) cells did not appear to be discriminatory in this study. Receiver operating characteristic (ROC) curve analysis showed that a combination of CD3 cell of < or = 45% and CD5 cell of < or = 55% was the best marker to identify DHF patients (sensitivity = 84% and specificity = 52% for CD3 cell of < or = 45%; sensitivity = 92% and specificity = 71% for CD5 cell of < or = 55%). CD4 cell of < or = 25% and CD8 cell < or = 30% were equally good in discriminating DHF from DF patients. On the other hand, the ROC curves indicated no clear difference between the immunoregulatory cell counts in DF from NDF Lymphopenia, atypical lymphocytosis and thrombocytopenia were significantly more evident in dengue compared to non-dengue infection but did not appear to be discriminatory among DHF and DF patients. The reduction in CD3, CD4, CD8, CD5 cells correlated with the degree of thrombocytopenia in DHF (p < 0.05) which suggests that these cells probably participate in a common pathogenetic mechanism.

Acute Disease↗
PubMed1993

Analysis of lymphocyte subsets in patients with aplastic anemia before and during immunosuppressive therapy.

To define the contribution of T-lymphocyte subsets in the development of aplastic anemia (AA), T-cell subpopulations including alpha beta T cells, gamma delta T cells, and delta TCS1-positive gamma delta T cells, were analyzed by cytophotometry in the peripheral blood (PB) and bone marrow (BM) of patients with AA before and after 6 weeks of therapy with anti-lymphocyte globulin (ALG), methylprednisolone, and cyclosporin A (CSA). In nine patients with AA a significant decrease of PB- and BM-derived T cells was observed after 6 weeks of therapy as compared with normal controls. At diagnosis, the CD4/CD8 ratio in PB and BM of the patients did not differ from the ratio in the control population; however, a reversed ratio (< 1) was present in PB as well as in BM after weeks of therapy. Interestingly, lymphocytes expressing the gamma delta T-cell receptor (TCR tau delta) were significantly decreased both before (PB 1.2 +/- 0.1%; BM 0.8 +/- 0.1%) and after 6 weeks of therapy (PB 0.7 +/- 0.1%; BM 0.7 +/- 0.1%) as compared with healthy controls (PB 2.4 +/- 0.2%; BM 2.3 +/- 0.2%). However, the proportion of the gamma delta-T-cell subpopulation expressing the delta TCS1 phenotype was markedly increased before (PB 42 +/- 3.5%; BM 31 +/- 3%) and especially after 42 days of therapy (PB 77 +/- 12%; BM 45 +/- 2%) as compared with that in normal subjects (PB 19 +/- 2%; BM 9.7 +/- 0.8%). At present, follow-up is under evaluation to correlate these findings with hematological response. The pathophysiological significance of the observed alterations within the T-cell subsets and especially the gamma delta T-cell populations will require further functional analyses, in particular since delta TCS1-positive gamma delta T cells exhibit autoimmunological capacity.

Anemia, Aplastic↗
PubMed1992

Lymphocyte proliferation and T-lymphocyte subsets during experimental immunomodulation of Balb/C mice by Olimunostim.

To objectivize possible immunomodulatory effects of polybacterial lysate Olimunostim (P. acnes, K. pneumoniae, S. aureus), splenic lymphocyte proliferation and T-lymphocyte subsets were followed-up in Balb/c mice administered perorally the lysate or saline (controls). The enhanced spontaneous lymphocyte proliferation observed at the beginning of Olimunostim application preceded a gradual increase of lymphocyte reactivity to T-mitogens reaching the maximum five days after the administration of the last dose and returning back to the control levels ten days afterwards. This stimulation of lymphocyte proliferation was accompanied by Olimunostim induced increase of CD4+ splenic lymphocytes being most pronounced five days after the end of immunomodulation and later returning to the initial values. The last experiment revealed an enhanced response of the in vivo primed lymphocytes after the re-exposure to Olimunostim in vitro. It is concluded that mostly nonspecific activation mechanisms, plausibly also parallelly induced specific immunity, are involved in Olimunostim modulatory effects on the cellular immune response.

Adjuvants, Immunologic↗
PubMed1996

Lymphocytes subsets in normal individuals: analysis by four color immunofluorescence and flow cytometry on whole blood.

In order to precisely define human lymphocytes subsets, we used four color immunofluorescence analysis and flow cytometry. We report here the results of systematic studies performed on whole blood from 20 normal volunteers. This was performed using monoclonal antibodies recognizing 18 different CD molecules and analyzed here into 14 different 4-color immunofluorescence combinations. This showed that among T cells, the two major CD3+CD8+ and CD3+CD8- subsets differed greatly in the percentage of cells expressing CD26, CD27, CD28, CD38, CD45RA, CD45RO, CD57, S6F1, BY55, CD101 and their respective combination representing an array of subsets. Furthermore the minor NK subsets, i.e. CD2+CD3-CD8+, CD2-CD3-CD8+, CD2+CD3-CD8-, CD2-CD3-CD8- also differed in percentages of cells expressing CD16, CD56, CD57, S6F1, BY55 and their combinations.

Antigens, CD↗
PubMed1982

T lymphocyte subsets in the duodenal epithelium in dermatitis herpetiformis.

Monoclonal antibodies to human T lymphocyte subsets and HLA-DR antigens were used to characterize the intra-epithelial T lymphocytes and HLA-DR reactive cells in the duodenal epithelium in dermatitis herpetiformis (DH). The expression of HLA-DR antigens on the epithelial cells was similar in patients and controls. There were significantly more Leu 2a (suppressor/ cytotoxic phenotype) reactive cells, as related to epithelial length, in 7 patients with DH than in the epithelium of 5 controls. However, the ratio of Leu 2a (suppressor/cytotoxic phenotype) to Leu 3a (helper/inducer phenotype) reactive cells was the same in the patients as in the controls. Thus this study indicates that there is a quantitative rather than a qualitative difference in T lymphocyte subpopulations in duodenal epithelium between patients with DH and normal persons.

Adult↗
PubMed1989

T lymphocyte subsets in the peripheral blood in patients with primary biliary cirrhosis.

T lymphocyte subsets and natural killer (NK) cells in the peripheral blood of 10 patients with primary biliary cirrhosis (PBC) were examined by using various kinds of monoclonal antibodies directed to the surface markers of the lymphocytes. We found that the population of Leu 2a+, Leu 15- cytotoxic T cells was decreased in PBC patients compared to normal controls, especially in those with a high serum titer of anti-mitochondria antibodies. However, there was no significant difference in the population of Leu 2a+, Leu 15+ suppressor T cells between PBC patients and normal controls. Although the population of Leu 3a+, Leu 8- helper T cells was not significantly different, the population of Leu 3a+, Leu 8+ suppressor-inducer T cells was remarkably increased in PBC patients compared to normal controls. On the other hand, no such difference was seen for the NK cells. Furthermore, the Leu 3a+/Leu 2a+ ratio was significantly higher in PBC patients especially in those with a high serum anti-mitochondria antibody titer, which was thought to be due to the decreased population of cytotoxic T cells.

Adult↗
PubMed1984

Regulation of normal human blood neutrophilic, macrophagic, and eosinophilic committed stem cell proliferation by autologous blood T lymphocyte subsets.

The influence of T lymphocyte (T cell) subsets on the proliferation of the blood neutrophilic, macrophagic, and eosinophilic cluster and colony (aggregate) forming cells (CFC) was evaluated. The T cells and the CFC-enriched B-null cells (mononuclear cells depleted of monocytes and T cells) and null cells (B-null) cells depleted of B lymphocytes) were separated from the blood of normal individuals. The population enriched for OKT4 (T4 cells) monoclonal antibody-binding T helper/inducer cells and for OKT8 (T8 cells) monoclonal antibody-binding T suppressor/cytotoxic cells were separated from the T cells or mononuclear cells depleted of monocytes by negative enrichment using an immunoadherence "panning" method. These separated cell populations were cultured separately, and the B-null or null cells were cocultured with the T, T4, and T8 cells in agar medium in the presence and absence of an exogenous source of colony-stimulating activity (CSA). The cultures were evaluated at day 14. The B-null and null cells, but not the T cells or subsets, contained CFC. The number of CFC proliferated from the B-null or null cells increased significantly (p less than 0.001) in cocultures with unseparated T and T8 cells in a dose-dependent manner. The T4 cells neither promoted nor inhibited the CFC growth. The T8 population was a better promoter (p less than 0.01) of CFC growth than the unseparated T cells. This suggests that the CFC promoting effect of the unseparated T cells is probably due to the influence of the T8 subset present within the T cells. The proportion of the neutrophilic, macrophagic, and eosinophilic CFC that proliferated in these cultures was comparable under the influence of the T and T8 cells. The results of these studies indicate that the T8 population, which is the suppressor in the classical immune system, promotes the growth of the blood CFC. We speculate that the T cells are involved in the regulation of granulopoiesis in vivo.

Cell Division↗
PubMed2005

Long-term kinetic of T-lymphocyte subsets in kidney-transplant recipients: influence of anti-T-cell antibodies and association with posttransplant malignancies.

A low CD4 lymphocyte count has been associated with skin and nonskin cancers in kidney transplant recipients (KTR) and might be a useful prediction tool. We analyzed the serial measurements of CD4 and CD8 lymphocytes to study the influence of immunosuppressants and look for a possible predictive value of lymphocyte count for the occurrence of cancer. In 250 successive KTR, blood lymphocytes were labeled for CD4 and CD8 count, prior transplantation, at month 3 and 6 and each year thereafter, throughout a 10-year observation period. The kinetics of lymphocyte subsets were compared in regard to treatments, cancer and confounding factors. ATG were responsible of an early and long lasting impairment in CD4 cells. Patients with a cancer and especially those with multiple tumors, presented with less CD4 cells throughout the observation period, but ATG were not directly associated to the occurrence of tumors. An early low CD4 count was of poor predictive value for the occurrence of cancer.

Adult↗
PubMed1991

[The profile of T-lymphocyte subsets' populations in 4 different kinds of pulmonary disorders].

By using the bronchoalveolar lavage (BAL) technique, the authors observed the distribution of T-lymphocyte subsets both in peripheral blood and BAL fluid from 4 different kinds of pulmonary disorders (44 cases). It was shown that the percentage of lymphocytes in BAL fluid was increased, the CD+3 and CD+4 cells were elevated and 4/8 ratio was also significantly elevated in the sarcoid patients (11 cases); the CD+4 cells decreased but the CD+8 cells increased and the 4/8 ratio decreased significantly in the patients of idiopathic pulmonary fibrosis (7 cases) and the patients with thoracic malignant tumors (20 cases). This special profile of T-lymphocytes indicates that the cell-mediated immune function may play an important role in the pathogenesis of the above illnesses.

Adult↗
PubMed2000

[Changes in lymphocyte subsets in bronchoalveolar lavage fluid in patients with systemic sclerosis].

The aim of this study was to estimate if alterations of lymphocyte subsets obtained by broncholaveolar lavage (BAL) were related to clinical data observed in nonsmoking patients with systemic sclerosis (SSc). Clinical examination included chest X-rays, spirometry and arterial blood gasometry. Patients were divided into group A (pulmonary changes present, n = 15) and B (without any changes, n = 7). Healthy subjects constituted the control group (n = 10). BAL lymphocytes were phenotyped using monoclonal antibodies coupling CD4, CD8 (both in coexpression with CD25), CD19 and HLA-DR human antigens and flow cytometer FACStar (Becton-Dickinson). Parallel staining was performed in peripheral blood. BAL lymphocyte typing was completed by BAL routine cytology. In SSc patients we found increased BAL total cell number, percentage of neutrophils, eosinophils and macrophage giant cells, as well as high percent of CD25+ and HLA-DR+ lymphocytes. In the group A neutrophilic alveolitis was observed in nearly half of cases: total lymphocyte number (per 1 ml of BAL fluid) and significantly reduced CD4/CD8 ratio were found. In the group B, as compared with controls, we found significantly elevated lymphocyte total cell number per 1 ml of BAL fluid (including particular subsets: CD3+, CD4+, CD8+). Also significantly high CD4+25+ lymphocyte percent was observed. Summing up, cytological and/or immunological alterations were observed in all examined SSc patients. The intensity of these alterations seems to be related to the clinical data. A decreased value of CD4/CD8 ratio may play a role in the local appearance of pulmonary changes in the course of systemic sclerosis.

Antibodies, Monoclonal↗
PubMed1991

Ontogeny of human lymphocytes. Two-color fluorescence analysis of circulating lymphocyte subsets in fetuses in the second trimester of pregnancy.

By using monoclonal antibodies, two-color immunofluorescence techniques and flow cytometry, we evaluated the surface marker phenotypes of lymphocyte subsets in cord blood samples from fetuses in the second trimester of pregnancy. The results indicate that cells of the T-, B- and NK-cell lineages as well as precursor cells can be detected in fetal blood at 18-20 weeks of gestation. At this stage of development, variable proportions of T and B lymphocytes express surface molecules, such as the CD1, CD10, CD38, CD45RA, indicative of a precursor or 'naive' state; on the other hand, the CD57 molecule is not detectable on the membrane of NK and T cells, and the RO isoform of the CD45 leukocyte antigen is synthesized by a low percentage of T cells. We suggest that the observed phenotypic peculiarities of the lymphoid cells might be related to the easy induction of tolerance that occurs in the early ontogenetic stages of the immune system.

Antigens, Differentiation↗
PubMed1983

Monoclonal antibody analysis of T-lymphocyte subsets in young and aged adults.

Eleven monoclonal antibodies identifying surface antigens present on human T lymphocytes were utilized to investigate the effects of advanced age on peripheral blood lymphocyte subsets. Both the proportion and number of lymphocytes recognized by five antibodies reactive with 'pan' T cell antigens (OKT3, OKT11, Leu4, T101 and Lyt3) decreased with age. The percentage of helper/inducer (OKT4+, Leu3a+) cells remained constant; however the proportion of Leu2a+, suppressor/cytotoxic cells declined. There was no change with age in the percent representation of OKT9+ or OKT10+ cells, nor in the ratio of helper/inducer to suppressor/cytotoxic cells (OKT4+/OKT8+ or Leu3a+/Leu2a+). Absolute numbers of helper/inducer (OKT4+, Leu3a+), suppressor/cytotoxic (OKT8+, Leu2a+), OKT9+ and OKT10+ cells were lower in elderly individuals as the result of lymphocytes constituting a lower percentage of the peripheral blood white cell population in this age group. While only small differences existed between the lymphocyte populations of young and aged men; aged women, compared to young women, had more dramatic shifts in their T cell populations. Comparison of antibodies putatively identifying similar (the same) functional groups of T cells demonstrated excellent correlation between the percentage of cells enumerated with the antibodies OKT3+: Leu4+ (r = .951), OKT4+: Leu3a+ (r = .914), OKT8+: Leu2a+ (r = .896), and in the ratio of helper/inducer to cytotoxic/suppressor OKT4+/OKT8+: Leu3a+/Leu2a+ (r = .926) cells.

Adult↗
PubMed2000

Differences between lymphocyte subsets, after allogeneic bone marrow transplantation, in patients who received tacrolimus and patients who received cyclosporin A.

The subsets of peripheral blood lymphocytes after allogeneic bone marrow transplantation were compared in 20 patients who received tacrolimus and 34 patients who received cyclosporin A (CsA) prophylactically. The phenotypes of CD3, CD4, CD8, and D8/CD57 were analyzed by flow cytometry. The percentage of CD3+ cells in the tacrolimus group (58.8% +/- 21.6%) was significantly lower than in the CsA group (77.2% +/- 12.8%) (P = .0239). The percentage of CD8+CD57+ cells in the patients receiving tacrolimus and developing acute graft-versus-host disease (GVHD) (grade I, 20.1% +/- 10.6%; grade II-IV, 13.2% +/- 6.3%) was significantly higher than in the patients receiving CsA and developing acute GVHD (grade I, 10.7% +/- 5.2%; grade II-IV, 7.7% +/- 4.0%) (grade I, P = .0036; grade II-IV, P = .0255). The absolute number of CD8+CD57+ cells in the patients with grade II-IV acute GVHD was also significantly higher in the tacrolimus group compared with the CsA group. There was no difference in the incidence of acute GVHD in the 2 groups. Recovery from acute GVHD in the tacrolimus group (16.6 +/- 13.6 days) was more rapid than in the CsA group (30.8 +/- 24.8 days) (P = .0124). These results suggest that, compared with CsA, tacrolimus administered prophylactically induces more CD8+CD57+ lymphocytes when acute GVHD occurs and accelerates the recovery from acute GVHD more rapidly.

Adolescent↗
PubMed2006

Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study.

BACKGROUND: Coronary atherosclerosis includes an activation of circulating T lymphocytes. Statins exert anti-inflammatory effects beyond lipid lowering. Whether these properties influence systemic T lymphocytes is unclear. METHODS: To investigate the effect of atorvastatin on circulating T-lymphocyte subsets producing proinflammatory and anti-inflammatory cytokines (interferon gamma [IFN-gamma(+)], interleukin 2 [IL-2(+)], IL-4(+), and IL-10(+)) and on the T-cell-activating soluble CD40 ligand (sCD40L), 30 hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. Eight healthy volunteers served as controls. Levels of peripheral cytokine-producing CD4+ and CD8+ T cells and their CD28- subsets were determined by FACS. Serum soluble CD40L was measured with ELISA. RESULTS: IL-2(+) T lymphocytes and sCD40L levels were higher in patients with CAD compared with controls, whereas IFN-gamma(+) and anti-inflammatory IL-4(+) and IL-10(+) T lymphocytes were similar. Levels of IL-2(+), IFN-gamma(+), IL-4(+), and IL-10(+) T-cell subsets as well as CD28- T lymphocytes were neither changed by atorvastatin nor by placebo, whereas sCD40L was lowered only in atorvastatin-treated patients (P < .01). CONCLUSION: Circulating IL-2(+) T lymphocytes are increased in patients with stable CAD reflecting an activation of the global immune system, but are not influenced by atorvastatin therapy. The elevated levels of platelet-derived T-lymphocyte-stimulating sCD40L are decreased by atorvastatin probably reflecting an atheroprotective effect. Hence, sCD40L may be an additional biomarker to be considered when evaluating the treatment effects of statins in patients with stable CAD.

Atorvastatin↗