Clonal analysis of CD4+/CD8+ T cells in a patient with aplastic anemia.
T cell clones were established from peripheral blood of a patient with severe aplastic anemia. 8 of 18 individual clonal T cell populations stably coexpressed CD4 and CD8 molecules, a phenotype characteristic for thymocytes and a minor subpopulation of circulating T lymphocytes. Analysis of T cell receptor genes revealed identical rearrangements of T cell receptor beta chain genes, suggesting clonality of these T cells. CD4+/CD8+ T cells clones were found to be efficiently cytotoxic towards autologous lymphoblasts. Autocytotoxicity could be blocked by a CD3 MAb, a MAb specific for monomorphic MHC class II determinants, and particularly, by an MHC-DP-specific MAb, suggesting specificity for autologous DP molecules. Perhaps more important, CD4+/CD8+ T cell clones inhibited differentiation of autologous progenitor enriched bone marrow cells in vitro by a direct cell-mediated mechanism. These data suggest that circulating cytotoxic CD4+/CD8+ T cell clones specific for autologous MHC-DP determinants may be involved in hematopoietic failure in some cases of aplastic anemia.
Moebius
U
U
Abteilung Angewandte Immunologie, Deutsches Krebsforschungszentrum, Heidelberg, FRG.
Herrmann
F
F
Hercend
T
T
Meuer
S C
SC
D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015329:Gene Rearrangement, T-Lymphocyte; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma