Equivalent helper functions of human "naive" and "memory" CD4+ T cells for the generation of alloreactive cytotoxic T lymphocytes.
Cells comprising the CD4+ T-cell population are heterogeneous with regard to function, maturation, and the expression of membrane molecules such as the CD45RA antigen. Previous analyses of the CD4+ subsets defined by CD45RA antigen expression have shown that the ability to provide help for antibody production is restricted to cells within the CD4+CD45RA- subset. In the present studies, we have examined the ability of "naive" CD4+CD45RA+ cells and "memory" CD4+CD45RA- cells to provide help for the generation of alloreactive CD8+ cytotoxic T lymphocytes. When purified CD4+CD45RA+ or CD4+CD45RA- cells were cultured with autologous CD8+ cells and allogeneic E- stimulator cells, both subsets were consistently able to provide help for CD8+ cytotoxic T-cell development. In contrast, the ability to provide help for antibody production was restricted to cells in the CD4+CD45RA- subset. Differences in the mechanisms of the helper functions for these two systems were also identified. Whereas exogenous interleukin-2 (IL-2) could replace the help provided by either CD4+ subset for cytotoxic T-cell generation, IL-2 had only minimal effects on immunoglobulin production. Thus, our studies highlight the contrasting cellular requirements and mechanisms involved in "help" for B-cell differentiation versus cytotoxic T-lymphocyte generation, and they show that the helper/inducer functions of human CD4+ cells are not mediated solely by the CD4+CD45RA- subset.
Yamashita
N
N
Department of Microbiology and Immunology, UCLA School of Medicine 90024.
Bullington
R
R
Clement
L T
LT
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D016827:CD8 Antigens; D002469:Cell Separation; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006649:Histocompatibility Antigens / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000502:physiology; D007700:Kinetics; D017493:Leukocyte Common Antigens; D008213:Lymphocyte Activation / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D006649:Histocompatibility Antigens; D007376:Interleukin-2; D017493:Leukocyte Common Antigens