Phenotypic and clonal analysis of T lymphocytes in childhood immune thrombocytopenic purpura.
In an attempt to identify and characterize T-lymphocyte immunoregulatory abnormalities in immune thrombocytopenic purpura (ITP), we have performed phenotypic and clonal analysis on peripheral T lymphocytes from 23 children with ITP. Quantitation of lymphocyte subpopulations showed that children with acute ITP had higher numbers of CD45RA+ and lower numbers of CD45RO+ T cells than children with chronic ITP or controls, but these differences may be age related. Analysis of T-cell receptor variable beta gene usage identified 2 boys with chronic ITP and elevated numbers of V beta 8+ T cells. Eight T-cell clones were established (6 CD4+, 4B4+ helper-inducer lines and 2 CD8+ lines) that showed in vitro proliferation against allogeneic platelets. The addition of autologous antigen-presenting cells enhanced the proliferation of six clones, but not for two clones that coexpressed natural killer (NK) markers. Four of seven positive clones also had measurable interleukin (IL)-2 secretion following platelet stimulation, providing further evidence for T-cell reactivity. Our results provide the first evidence that patients with ITP may have platelet-reactive T lymphocytes identifiable at the clonal level, supporting the hypothesis that autoreactive peripheral T lymphocytes may mediate or participate in the pathogenesis of this disorder.
Ware
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Department of Pediatrics, Duke University Medical Center, Durham, NC 27710.
Howard
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D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000032:analysis*; D001792:Blood Platelets / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis / Q000097:blood; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism
D015703:Antigens, CD; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA; D013936:Thymidine