Enhancement of IL-2-induced T cell proliferation by a novel factor(s) present in murine spleen dendritic cell-T cell culture supernatants.
The mechanism(s) underlying the potent accessory cell function of dendritic cells (DC) remains unclear. The possibility was considered that a soluble factor(s) released during the interaction of DC and T cells might contribute to the potent T cell activating function of DC. Culture supernatants were generated from mixtures of murine spleen DC and periodate-treated spleen T cells and were examined for the presence of known cytokine activities and factors capable of enhancing T cell responsiveness to IL-2. Serum-free supernatants from 24 h DC-T cell co-cultures exhibited high levels of IL-2, detectable levels of IL-3, and negligible levels of IL-1, -4, -5, -6, and TNF. A factor(s) was also identified with an apparent Mr of 12.5 to 17.0 kDa, henceforth designated IL-2 enhancing factor (IL-2EF), which enhanced the IL-2-induced proliferation of murine thymocytes, CTLL, and HT-2 cells by approximately three- to fourfold. This enhancement was also observed in the presence of neutralizing antibodies to murine IL-1 alpha, -1 beta, -3, -4, -5, -6, granulocyte-macrophage (GM)-CSF, TNF, and IFN-gamma. However, IL-2EF failed to enhance: 1) the activity of IL-1, -3, -4, -5, or -6 on cells responsive to these cytokines; 2) IL-2-augmented, IL-5-induced BCL1 proliferation; and 3) either PHA- or Con A-stimulated thymocyte proliferation. Moreover, neither IFN-gamma nor GM-CSF exhibited IL-2EF activity. When DC and T cells were cultured separately (after an initial 12 h co-culture period), IL-2EF activity resided predominantly in the T cell-derived supernatants. These and other data indicate that IL-2EF, a heat-labile T cell-derived 12.5 to 17.0 kDa protein, is distinct from IL-1 alpha, -1 beta, -2, -3, -4, -5, -6, TNF, IFN-gamma, GM-CSF, and previously described factors that co-stimulate thymocyte proliferation in the presence of Con A or PHA. It is suggested that IL-2EF functions to specifically enhance IL-2-driven T cell proliferation and contributes to the potent activation of T cells induced by DC.
Everson
M P
MP
Department of Medicine, University of Alabama, Birmingham 35294.
Spalding
D M
DM
Koopman
W J
WJ
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000302:isolation & purification / Q000502:physiology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001685:Biological Factors / Q000302:isolation & purification / Q000502:physiology; D002450:Cell Communication; D002474:Cell-Free System; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016207:Cytokines; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004357:Drug Synergism; D007375:Interleukin-1; D007376:Interleukin-2; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D013154:Spleen; D013347:Subcellular Fractions; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D007376:Interleukin-2