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.