Age-related changes in human blood lymphocyte subpopulations

Erkeller-Yuksel, Feza; Deneys, Véronique; Yüksel, B.; Hannet, I.; Hulstaert, Frank; Hamilton, Carly; MacKinnon, Heather; Turner-Stokes, Lynne; Munhyeshuli, V.; Vanlangendonck, Francis; Bruyère, Marc De; Bach, Bruce Allen; Lydyard, PM

doi:10.1016/s0022-3476(05)80430-5

Cited by 355 publications

(221 citation statements)

References 29 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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“…20 Table 1 shows that the mean and median age of the individuals in the proband Ia group (and the proband II/III group) was lower than that of the other groups (including the HC group). Two approaches were used to ascertain if immunophenotypic alterations were influenced by age.…”

Section: The Influence Of Age On Immunophenotypic Findingsmentioning

confidence: 91%

Immunophenotypic profiles in families with autoimmune lymphoproliferative syndrome

Bleesing

Brown

Straus

et al. 2001

Blood

125

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“…For reference values, normal leukocyte and lymphocyte counts and relative percentages are provided in Table 1. 15,16 Lymphocyte subpopulations were analyzed by flow cytometry with three-color analyses. Peripheral blood lymphocytes were stained with PerCP (PCP)-labeled anti-CD45 monoclonal antibody and leukocytes were gated by forward and side scatter parameters.…”

Section: Lymphocyte Analysesmentioning

confidence: 99%

Profound abnormality of the B/T lymphocyte ratio during chemotherapy for pediatric acute lymphoblastic leukemia

et al. 1998

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The fluorescence-activated cell sorter (FACS) was utilized to phenotype lymphocyte compartments in children receiving intensive chemotherapy for acute lymphoblastic leukemia (ALL). Sixteen patients (eight males and eight females) of diverse ages, risks of relapse, and within weeks 7-53 of maintenance/continuation chemotherapy treatment were arbitrarily selected for study. All 16 patients had profound B cell lymphopenia. In contrast, T cell numbers were often normal or marginally low, and accounted for up to 98% of the lymphocyte populations. No abnormality in T cell phenotypes could be demonstrated. Due to the highly skewed B/T lymphocyte ratios in these ALL patients, the absolute white blood cell counts and lymphocyte percentages were not predictive of the underlying B cell lymphopenia. Patients were also tested for serum immunoglobulin levels and most had abnormally low IgG and IgM. None of four patients immunized with the 1996-1997 influenza virus vaccine seroconverted to at least two vaccine antigens as compared to 10 of 10 healthy, age-matched controls. In total, these data highlight for the first time the profound abnormality of the B/T lymphocyte ratio in patients during treatment for ALL, and argue for consideration of B cell-targeted immunotherapy.

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Age-related changes in human blood lymphocyte subpopulations

Cited by 355 publications

References 29 publications

Genetic influence on peripheral blood T lymphocyte levels

Genetic influence on peripheral blood T lymphocyte levels

Immunophenotypic profiles in families with autoimmune lymphoproliferative syndrome

Profound abnormality of the B/T lymphocyte ratio during chemotherapy for pediatric acute lymphoblastic leukemia

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