Down syndrome (DS) peripheral blood contains phenotypically mature CD3+TCR alpha, beta+ cells but abnormal proportions of TCR alpha, beta+, TCR gamma, delta+, and CD4+ CD45RA+ cells: evidence for an inefficient release of mature T cells by the DS thymus.
Down syndrome (DS) thymocytes have a markedly diminished proportion of cells expressing high levels of the alpha, beta T cell receptor (TCR alpha, beta) and the associated CD3 molecule. Thus, we examined the surface expression of TCR alpha, beta and CD3 as well as TCR gamma, delta, CD4, CD8, CD16, and CD45RA on peripheral blood lymphocytes (PBL) from 13 noninstitutionalized subjects with DS and 13 closely age-matched sibling controls using immunofluorescence and flow cytometry. DS PBL expressed high surface levels of TCR alpha, beta and CD3, but, as compared to controls, they had a lower proportion of cells expressing TCR alpha, beta (61% vs. 68%, respectively; P less than or equal to 0.05). Moreover, the absolute number of TCR alpha, beta+ cells was considerably lower for DS subjects than for controls (1634 +/- 229 vs. 2763 +/- 530, respectively; P less than or equal to 0.05). DS subjects had a markedly higher proportion of cells expressing TCR gamma, delta than did the controls (12% vs. 7%, respectively; P less than or equal to 0.02). In addition, DS subjects had a lower proportion of CD4+CD45RA+ cells than controls (22% vs. 35%, respectively; P less than or equal to 0.02), representing naive T cells which have recently emigrated from the thymus. The imbalance in the proportions of T cell subpopulations we have observed in DS PBL may contribute to the increased susceptibility to infection associated with DS and may represent a diminished efficiency in the production of newly differentiated T cells by the DS thymus.
Murphy
M
M
Department of Pediatrics, University of California, San Francisco 94143.
Epstein
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LB
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000032:analysis*; D000943:Antigens, Differentiation / Q000032:analysis*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis* / Q000235:genetics; D017252:CD3 Complex; D015704:CD4 Antigens / Q000032:analysis*; D016827:CD8 Antigens / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004314:Down Syndrome / Q000235:genetics* / Q000276:immunology; D004804:Eosinophils / Q000166:cytology; D006649:Histocompatibility Antigens / Q000032:analysis*; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens; D007958:Leukocyte Count; D008214:Lymphocytes / Q000166:cytology; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D011961:Receptors, Fc / Q000032:analysis*; D017452:Receptors, IgG; D013950:Thymus Gland / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011961:Receptors, Fc; D017452:Receptors, IgG; D017493:Leukocyte Common Antigens