Sequential effects of prostaglandins and interferon-gamma on differentiation of CD8+ suppressor cells.
We have previously demonstrated that differentiation of CD8+ Tp44- suppressor cells in pokeweed mitogen (PWM)-stimulated cultures requires soluble factors elaborated by CD4+ cells and monocytes, and that the monocyte signal for such differentiation can be replaced by prostaglandin E2 (PGE2). In this study, we explored the ability of interleukin 2 (IL 2) and interferon-gamma (IFN-gamma) to replace the CD4+ signal. When IL 2 or IFN-gamma was used at concentrations equivalent to those present in supernatants of PWM-pulsed cultures of CD4+ cells, no effect on differentiation of CD8+ cells was observed. However, a potent suppressor inducing activity was detected when IFN-gamma, but not IL 2, was mixed with supernatants derived from cultures of PWM-pulsed purified monocytes (M phi sup) or with 10(-8) M PGE2. Differentiated CD8+ suppressor cells (Ts) inhibited both PWM-stimulated proliferative response of CD4+ cells and immunoglobulin production by B cells. The signals mediated by the M phi sup or PGE2 and IFN-gamma were shown to act sequentially. That is, M phi sup or PGE2 was required initially, followed by an IFN-gamma-dependent differentiative step. These studies thus suggest a cascade of cellular interactions involving monocytes, CD4+ cells, and CD8+ Ts precursors that are required for the differentiation of CD8+ suppressor effector cells.
D000917:Antibody Formation / Q000187:drug effects; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects*; D015232:Dinoprostone; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000502:physiology; D011043:Pokeweed Mitogens / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D007376:Interleukin-2; D011043:Pokeweed Mitogens; D011458:Prostaglandins E; D007371:Interferon-gamma; D015232:Dinoprostone