Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia.
Chronic autoimmune thrombocytopenic purpura (ATP) is a common hematologic disorder in which platelet-specific autoantibodies bind to platelets and enhance their destruction by the reticuloendothelial system. While there has been considerable investigation of the humoral immune abnormalities in ATP, little work has been performed on the cellular immunoregulatory aspects of this autoimmune disorder. We describe here that patients with ATP have lymphocytes that proliferate normally when stimulated by mitogens. However, when stimulated by normal control platelets in 7-day antigen-presenting cell cultures, peripheral blood mononuclear cells (PBMC) from patients with ATP proliferate at significantly higher levels (P less than .001) and their lymphocytes secrete significantly higher amounts of interleukin-2 (IL-2) (P less than .001) than do lymphocytes from control subjects. Depletion studies with monoclonal anti-CD8 and complement did not reduce the proliferative capacity of the responding PBMC population, indicating that CD4+ T-helper cells may be responsible for the response. Phenotypic analysis of peripheral blood lymphocyte subsets from patients with ATP showed that there was a significant reduction in CD4+Leu8+ T suppressor-inducer cells (P less than .001) and a concomitant increase in CD3+DR+ activated T cells (P less than .001) and CD19+ B cells (P less than .05). These data indicate that CD4+ T-helper cells from patients with ATP are stimulated by normal platelet antigen(s) to secrete IL-2 and may modulate the enhanced antiplatelet autoantibody response.
Semple
J W
JW
Department of Immunohematology, St Michael's Hospital, Toronto, Ontario, Canada.
Freedman
J
J
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001792:Blood Platelets / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D010641:Phenotype; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood* / Q000276:immunology; D012016:Reference Values; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D015703:Antigens, CD; D016827:CD8 Antigens; D007376:Interleukin-2; D003165:Complement System Proteins