Human CD8+ lymphocytes stimulated in the absence of CD4+ cells enhance IgG production by antibody-secreting B cells

We describe conditions where the addition of stimulated CD8+ lymphocytes from healthy donors to autologous antibody-secreting B cells significantly enhanced IgG production by these cells. In two-step experiments, purified CD8+ lymphocytes were first cocultured with irradiated allogeneic monocytes. These cells developed interleukin 2 receptors, but proliferated only minimally in the absence of CD4+ cells. When added to antibody-secreting B cells, these CD8+ lymphocytes augmented IgG production in a dose-dependent manner in comparison with control CD8+ cells. Studies with T killer cell precursors revealed an inverse correlation between augmentation of antibody synthesis and the generation of MHC class I-restricted cytotoxic activity against lymphocytes from the allogeneic donor. Evidence is presented that CD8+ CD45RA+ CD45RO- can provide B cell help, whereas the generation of CD8+ CD45RA+ CD45RO+ cells inhibits this helper activity. Our studies support the hypothesis that in chronic diseases characterized by CD4+ cell hypofunction, CD8+ cells not only fail to down-regulate antibody production, but can provide B cell help.