Trypanosoma cruzi-induced suppression of IL-2 production. I. Evidence for the presence of IL-2-producing cells.
Mice infected with the protozoan parasite Trypanosoma cruzi, the causative agent of human Chagas' disease, are profoundly immunodepressed in their response to various Ag and mitogens. A key factor in this immunosuppression is the essential inability to produce the T cell growth factor IL-2. In this study we demonstrate that this failure to produce IL-2 in response to mitogen stimulation is not the result of the absence of production of soluble or membrane-bound IL-1 by macrophages. Limiting dilution analysis of the precursor frequency of IL-2 producers suggests that an adequate number of precursors for IL-2 production are present in the spleens of infected mice, but that their activity may be regulated by suppressor cells. The presence of precursor cells for IL-2 production is supported by experiments showing that the combination of calcium ionophores and PMA elicits IL-2 production by spleen cells from both normal and T. cruzi-infected mice. Although Con A can provide either of the signals necessary for IL-2 production, calcium flux or protein kinase C activation, to T cells from normal mice, Con A in combination with either calcium ionophore or phorbol ester failed to activate T cells from infected mice to produce IL-2. Preculture of spleen cells from infected mice for 48 to 72 h before addition of Con A results in near normal production of IL-2. This recovery of the capacity to produce IL-2 does not occur if parasite Ag is present during the preculture period. These results suggest that the inability of T cells from T. cruzi-infected mice to produce IL-2 in vitro in response to Con A is not due to the lack of IL-2-producing cells, but may be the result of the maturational state of the T cells or to the presence of a suppressor population.
Tarleton
R L
RL
Department of Zoology, University of Georgia, Athens 30602.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D014355:Chagas Disease / Q000276:immunology*; D003208:Concanavalin A / Q000494:pharmacology; D004987:Ethers / Q000494:pharmacology; D005260:Female; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000096:biosynthesis*; D015759:Ionomycin; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000378:metabolism; D013154:Spleen / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000502:physiology*
D004987:Ethers; D007376:Interleukin-2; D003208:Concanavalin A; D000001:Calcimycin; D015759:Ionomycin; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium