Differential effects of Trypanosoma cruzi on the transcription of the p55IL-2R, c-fos, c-myc and CD69 genes in activated human lymphocytes.
Mitogen-activated lymphocytes co-cultured with either purified Trypanosoma cruzi trypomastigotes or the filtrate of trypomastigote suspensions in culture medium manifest a significant decrease in their capacities to express p55 interleukin-2 receptor molecules (p55IL-2R) on their membrane and proliferate. In this study we found that the cytoplasmic levels of p55IL-2R are also markedly reduced under these conditions. This inhibition appeared to result from altered gene transcription since the levels of p55IL-2R mRNA in phytohaemagglutinin (PHA)-stimulated human peripheral blood mononuclear cells (PBMC) dropped substantially in the presence of parasite suspension filtrate. The rates of decay for p55IL-2R mRNA determined in cultures lacking and containing the parasite filtrate after addition of actinomycin D to inhibit further RNA synthesis were comparable. These results indicated that decreased p55IL-2R mRNA was not due to decreased stability of this mRNA under our conditions and pointed to a transcriptional or pre-transcriptional modification as the likely mechanism by which T. cruzi affects activated lymphocytes. The parasite filtrate did not appear to affect transcription of c-fos or c-myc (known to occur in the very early stages of lymphocyte activation) or that of CD69 (which is concomitant with p55IL-2R transcription). Thus, decreased p55IL-2R gene transcription appears to be a somewhat selective effect of a T. cruzi-derived molecule(s) rather than the consequence of an overall shutdown of gene transcription.
Kierszenbaum
F
F
Department of Microbiology, Michigan State University, East Lansing 48824-1101, USA.
Majumder
S
S
Mejia Lopez
H
H
Sztein
M B
MB
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology; D005434:Flow Cytometry; D016762:Genes, fos / Q000187:drug effects / Q000276:immunology*; D016259:Genes, myc / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008813:Mice, Inbred ICR; D010835:Phytohemagglutinins / Q000494:pharmacology; D015800:Protozoan Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D010835:Phytohemagglutinins; D015800:Protozoan Proteins; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D000099192:CD69 Antigens