Developmental and maturational changes in human blood lymphocyte subpopulations

Hannet, I.; Erkeller-Yuksel, Feza; Lydyard, Peter M.; Deneys, Véronique; DeBruyère, M.

doi:10.1016/0167-5699(92)90157-3

Cited by 375 publications

(233 citation statements)

References 26 publications

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“…Absolute numbers of lymphocytes, CD3 + T cells, CD4 + T cells and CD8 + T cells and CD4:CD8 ratios all declined with age. 6,[9][10][11][12] It has been previously reported that the CD4:CD8 ratio in inbred mice, strains of rat, and humans is under genetic control. In the mouse the ratio was concluded to be under the control of a single dominant gene and significantly influenced by age.…”

Section: Discussionmentioning

confidence: 99%

Genetic influence on peripheral blood T lymphocyte levels

Ahmadi

Norman

et al. 2000

Genes Immun

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T lymphocytes are a major component of the adaptive immune system. CD4 positive T cell subpopulations regulate B cell and macrophage effector function while CD8 positive T cells are largely responsible for anti-viral cytotoxic activity. The degree of natural variation in the levels and ratios of the various T cell subpopulations is a possible risk factor for the development of autommune disease, infectious disease and cancer. There is some evidence from studies of inbred strains of mice and humans which suggests that variation in T cell subpopulations is genetically influenced. However, family studies alone cannot distinguish between common environmental and shared genetic influences and provide less robust estimates of the heritability than twin studies. To comprehensively examine genetic influences on a selection of important T cell phenotypes, we investigated variation in levels of total lymphocytes, CD3 + , CD4 + , CD8 + , CD3 + CD4 + , CD3 + CD8 + lymphocytes and in CD4:CD8 ratio as a proportion of lymphocytes and of T cells using the classical twin model approach. Healthy female twin pairs were sampled from the St. Thomas' UK Adult Twin Registry. A maximum of 103 monozygotic (MZ) and 186 dizygotic (DZ) twins aged 18-80 years participated in the study. Whole blood samples were analysed for T cell subsets by flow cytometry. The relative genetic contribution to these phenotypes was estimated using a variance components model-fitting approach. Heritability estimates were calculated of 65% for CD4:CD8 T cell and lymphocyte ratios, around 50% for absolute lymphocyte, CD3 + and CD4 + counts, and 56% for CD8 + numbers. Unique (rather than shared) familial environment explains the remainder of the variance. Genetic factors have a major influence on the variation in peripheral T cell subset numbers. Polymorphism dictating such variation should be taken into account when assessing risk factors for T cell immune-mediated disease with a genetic background. Genes and Immunity (2000) 1, 423-427.

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Section: Discussionmentioning

confidence: 99%

Genetic influence on peripheral blood T lymphocyte levels

Ahmadi

Norman

et al. 2000

Genes Immun

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“…5 CD57 + T cells constitute a minor fraction of lymphocytes in healthy individuals. 6 Aberrant expansions of CD57 + T cells have been associated with a number of clinical disorders, including human immunodeficiency virus (HIV) or human cytomegalovirus infection, allotransplantation, rheumatoid arthritis, inflammatory bowel diseases, common variable immunodeficiency, congenital clotting disorders and Down's syndrome. 7 CD8 + CD57 + lymphocytes from normal subjects inhibit pokeweed mitogen driven B cell differentiation, proliferation and immunoglobulin (Ig) production [8][9][10] in a contactdependent manner, 10 and they exhibit lectin-dependent and anti-CD3 redirected cytotoxic activity, 11 as well as antigenspecific cytotoxicity.…”

Section: Introductionmentioning

confidence: 99%

CD57+/CD28− T cells in untreated hemato-oncological patients are expanded and display a Th1-type cytokine secretion profile, ex vivo cytolytic activity and enhanced tendency to apoptosis

et al. 1998

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Three-color flow cytometry immunophenotyping revealed significant increases of CD57 + and CD28 − cells among both circulating CD4 + and CD8 + T lymphocytes of untreated hemato-oncological patients (n = 54) as compared to healthy donors (n = 55), with CD57 and CD28 expression on the patients' T cells being largely reciprocal. Marked expansion of CD57 + cells among circulating CD4 + T lymphocytes was frequently detected in patients with chronic leukemia of B cell origin (B-CLL, hairy cell leukemia) but not in patients with chronic myeloid leukemia, suggesting a causal relation with the tumor's major histocompatibility complex class II expression. Using immunomagnetic separation techniques, we further demonstrate that the patients' CD57 + /CD28 − T cells display a typical Th1-type cytokine secretion profile upon anti-CD3 stimulation, with a markedly higher secretion of the Th1-type cytokines IL-2, IFN-␥, and TNF-␣ than their CD57 − /CD28 + counterparts. Cytotoxic activity of circulating CD8 + T lymphocytes, measured ex vivo in an anti-CD3-redirected assay, was almost exclusively exerted by the CD57 + /CD28 − subset. Moreover, a marked cytotoxic activity was detected within CD4 + CD57 + T cells from some B-CLL patients. Finally, the patients' CD57 + /CD28 − T cells displayed an increased tendency to apoptosis in culture. Collectively, our results indicate that the expanded CD57 + /CD28 − T cells in hemato-oncological patients represent differentiated effector cells, similar to their (quantitatively minor) counterpart in healthy donors. The reason for their expansion and their pathophysiologic significance, however, remains unclear.

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“…Recently, increasing proportions of CD3 + T cells expressing CD57 (80% of which coexpress CD8) have been related to the duration of RA disease (26). However, other groups have reported a gradual increase in CD57 expression on CD8+ cells with age, ranging from none in neonates to >25% in healthy adults (27). No previous direct comparison has been made between RA patients and age-matched controls.…”

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confidence: 96%

Cd8^high+ (CD57+) T cells in patients with rheumatoid arthritis

Wang

Lawson

Vedhara

et al. 1997

Arthritis & Rheumatism

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Objective. To investigate the development and T cell receptor (TCR) usage of CD8+, CD57+ T cells in rheumatoid arthritis (RA) patients.Methods. Three-color flow cytometry using monoclonal antibodies (MAb) to CD8, CD57 and different TCR V, gene products.Results. The proportion of CD8+ T cells expressing CD57 (CD57/CDS) was significantly higher in RA patients compared with age-matched controls. Expanded TCR V, populations were more frequent, and were found in both RA patient-derived CDShigh+ (CD57+) and CDS+, CD57-populations. TCR V,5+ and TCR V,13+ expansions were present at high frequency (5 of 26 and 7 of 26, respectively). TCR V, expansions in CDShigh+ (CD57+) lymphocytes from RA patients were significantly larger than those in age-matched controls (expansion index 2.38 f 0.28, n = 41 and 1.63 f 0.09, n = 32, respectively), and were stable over time.Conclusion. RA leads to an increase in the frequency of expanded CD8+ T cell subsets expressing selected TCR, due to expansion of TCR V,+ populaPreliminary data from this study were presented as a poster at the 9th International Immunology Congress, San Francisco, California, 1995.

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Developmental and maturational changes in human blood lymphocyte subpopulations

Cited by 375 publications

References 26 publications

Genetic influence on peripheral blood T lymphocyte levels

Genetic influence on peripheral blood T lymphocyte levels

CD57+/CD28− T cells in untreated hemato-oncological patients are expanded and display a Th1-type cytokine secretion profile, ex vivo cytolytic activity and enhanced tendency to apoptosis

Cd8^high+ (CD57+) T cells in patients with rheumatoid arthritis

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Developmental and maturational changes in human blood lymphocyte subpopulations

Cited by 375 publications

References 26 publications

Genetic influence on peripheral blood T lymphocyte levels

Genetic influence on peripheral blood T lymphocyte levels

CD57+/CD28− T cells in untreated hemato-oncological patients are expanded and display a Th1-type cytokine secretion profile, ex vivo cytolytic activity and enhanced tendency to apoptosis

Cd8high+ (CD57+) T cells in patients with rheumatoid arthritis

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Cd8^high+ (CD57+) T cells in patients with rheumatoid arthritis