Selective suppressive effects of Trypanosoma cruzi infection on IL-2, c-myc, and c-fos gene expression.
Infection with Trypanosoma cruzi is accompanied by a profound suppression of immune responses including the production of IL-2. Previous experiments have confirmed a correlated decrease in IL-2 mRNA levels in lymphoid cells from infected mice. To further define the molecular basis of this regulation, we have examined the production and degradation of mRNA for IL-2 and other T cell activation genes in cells from T. cruzi-infected mice. Spleen cells from C57BL/6J mice infected with the Brazil strain of T. cruzi were analyzed for the kinetic expression of IL-2, IL-2R alpha, c-myc, and c-fos genes in response to Con A and PMA costimulation. Cells from infected mice exhibited a selective reduction of c-myc and c-fos mRNA in association with the severe suppression of the IL-2 gene, but a less severe to comparable production of IL-2R alpha mRNA compared with normal spleen cells. The similar patterns of the suppression of c-myc and IL-2 mRNA suggest a common mechanism of down-regulation of these two genes in T. cruzi infection. Actinomycin D treatment was used to demonstrate that decreased steady state levels of IL-2, c-myc, and c-fos mRNA in cells from infected mice were not due to an increased rate of degradation of these mRNA. Cycloheximide treatment enhanced the expression of IL-2, IL-2R alpha, c-myc, and c-fos mRNA in spleen cells from both normal and infected mice. Although a larger percentage of induction was observed in cells from infected mice, the mRNA levels for IL-2, c-myc, and c-fos in cells from infected mice were still lower than those of normal cells. Spleen cells from infected mice precultured for 24 to 72 h before the addition of mitogens showed significant enhancement of IL-2 and c-myc gene expression; however, this recovery was inhibited if fixed T. cruzi was present in the preculture medium. These data suggest that the reduction of IL-2 mRNA in infected mice is not the result of an increased degradation of its mRNA but to down-regulation of transcription of the IL-2 gene in T cells from T. cruzi-infected mice. Preculture-induced recovery of IL-2 production appears to result from release from this regulation and full expression of the IL-2 gene.
Soong
L
L
Department of Zoology, University of Georgia, Athens 30602.
Tarleton
R L
RL
D000818:Animals; D014355:Chagas Disease / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D016762:Genes, fos; D016259:Genes, myc; D007108:Immune Tolerance; D007376:Interleukin-2 / Q000235:genetics*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013154:Spleen / Q000166:cytology; D014349:Trypanosoma cruzi
D007376:Interleukin-2; D015375:Receptors, Interleukin-2