IL-10: a novel cytotoxic T cell differentiation factor.
A previous report concluded that a new cytokine, designated IL-10, is a growth cofactor for thymocytes, spleen, and lymph node cells. In this report, we have focused on the effects of IL-10 on CD8+ spleen T cells. We first observed that IL-10 enhances the growth of CD8+ T cells to IL-2. We then investigated the effect of murine rIL-10 on the induction of murine effector CTL from CTL precursors (CTL-p) using both bulk and filler cell-free limiting-dilution cultures. IL-10 alone could not induce Con A-activated FACS-sorted CD8+ T cells either to proliferate or to generate effector CTL. In combination with IL-2, however, IL-10 augmented the cytolytic activity of effector CTL generated from Con A-activated spleen CD8+ T cells in bulk cultures incubated for 5 days. In limiting-dilution cultures (using solid-phase anti-CD3 mAb as stimulus), IL-10, in combination with IL-2, substantially increased the CTL-p frequency and augmented the cytolytic activity per clone expanded from one CD8+ T cell when compared with cells cultured in IL-2 alone. Kinetic studies showed that IL-10 is required at both early and late culture stages for optimal generation of effector CTL. The potentiating effects of IL-10 on CTL function were neutralized by an anti-IL-10 mAb. These results indicate that IL-10 has direct effects on mature T cells, and suggest that IL-10 also functions as a cytotoxic T cell differentiation factor, which promotes a higher number of IL-2-activated CTL-p to proliferate and differentiate into effector CTL. In contrast, IL-10 did not enhance significantly the lymphokine-activated killer cell activity of IL-2-grown CD8+ cytotoxic T cells.
Chen
W F
WF
Department of Immunology, DNAX Research Institute, Palo Alto, CA 94304.
Zlotnik
A
A
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D016827:CD8 Antigens; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D066298:In Vitro Techniques; D016753:Interleukin-10; D007376:Interleukin-2 / Q000502:physiology; D007378:Interleukins / Q000494:pharmacology / Q000502:physiology*; D015979:Killer Cells, Lymphokine-Activated / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008808:Mice, Inbred CBA; D016176:T-Lymphocyte Subsets / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology*
D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D007376:Interleukin-2; D007378:Interleukins; D016753:Interleukin-10