Trypanosoma cruzi-induced suppression of IL-2 production. II. Evidence for a role for suppressor cells.
Suppression of IL-2 production during experimental Chagas' disease accounts at least in part for the overall depressed state of the immune system in infected mice. The failure to produce IL-2 in response to mitogen stimulation is not the result of the lack of cells capable of producing IL-2, but appears to be due to regulation of IL-2 production by suppressor cells. This conclusion is supported by cell-mixing experiments where the ability of cells from infected mice to suppress normal spleen cell IL-2 production is evident. Although depletion of plastic and Sephadex G-10 adherent cells results in modest increases in IL-2 production by spleen cells from infected mice, even in the presence of normal adherent cells as a source of IL-1 producers, IL-2 production does not approach normal levels. Also, isolated macrophages are not by themselves suppressive for normal spleen cell IL-2 production, whereas plastic and G-10 nonadherent cells from infected mice are. Depletion of Thy-1+ and Ly-2+ cells not only completely abrogates the ability of spleen cells from infected mice to suppress normal IL-2 production, but results in a cell preparation which actually enhances IL-2 production. Anti-Ly-2 and C treatment of infected spleen cells also markedly enhances their ability to produce IL-2. These results indicate a major role for Ts cells in the regulation of IL-2 production, and a relatively minor role of macrophages as direct effector cells of suppression in this response. The ability to enhance IL-2 production in this system with PG synthesis inhibitors suggests a role for PG-producing cells such as macrophages in the suppressor mechanism, perhaps as inducers of the suppressor effector cells.
Tarleton
R L
RL
Department of Zoology, University of Georgia, Athens 30602.
D000818:Animals; D002469:Cell Separation / Q000379:methods; D014355:Chagas Disease / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis*; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D011453:Prostaglandins / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000502:physiology*
D007376:Interleukin-2; D011453:Prostaglandins