In vitro simulation of immunosuppression caused by Trypanosoma brucei: active involvement of gamma interferon and tumor necrosis factor in the pathway of suppression.

摘要: Experimental infections of mice with the African trypanosome Trypanosoma brucei lead to a profound state T-cell unresponsiveness in lymph node cell (LNC) compartment. This suppression is mediated by macrophage-like cells which inhibit interleukin 2 (IL-2) secretion and down-regulate IL-2 receptor expression (M. Sileghem, A. Darji, R. Hamers, M. Van de Winkel, P. De Baetselier, Eur. J. Immunol. 19:829-835, 1989). Similar suppressive can be generated vitro pulsing 2C11-12 macrophage hybridoma opsonized T. parasites (2C11-12P cells). Cocultures 2C11-12P LNCs secrete higher levels gamma interferon (IFN-gamma), hyperproduction IFN-gamma was found confined CD8+ lymphoid cells. Elimination from cocultures restores proliferative response. Furthermore, addition neutralizing anti-IFN-gamma antibodies reduces level concomitantly expression. Hence, plays cardinal role this model for brucei-elicited immunosuppression. two-chamber culture system further demonstrated that cell-cell contact required and, moreover, cooperates 2C11-12P-derived diffusible factor exert its activity. Finally, tumor necrosis alpha (TNF-alpha produced implicated IFN-gamma, since anti-TNF-alpha reduced abrogated IFN-gamma. Collectively, our findings indicate differentially influence subpopulations: (i) are signaled via produce TNF-alpha process, (ii) locally macrophage-released factors act concert CD4+ responses.