Inhibitory effects of the Trypanosoma cruzi membrane glycoprotein AGC10 on the expression of IL-2 receptor chains and secretion of cytokines by subpopulations of activated human T lymphocytes.
The Trypanosoma cruzi membrane glycoprotein AGC10 has been shown to alter some human macrophage functions (De Diego, J. L. et al., J. Immunol. 1997. 159: 4983-4989). We show here that, in the presence of AGC10, [3H]thymidine incorporation by normal human lymphocytes stimulated with anti-CD3 or phytohemagglutinin (PHA) is severely curtailed. This effect was found to involve down-regulation of the expression of both CD25 (IL-2R alpha) and CD122 (IL-2R beta) on the lymphocyte membrane and a marked decrease in the level of up-regulation of the expression of surface CD132 (IL-2R gamma or gamma(c)). These alterations occurred in fairly large proportions of CD4+ and CD8+ lymphocytes. AGC10 also inhibited proliferation and expression of IL-2 receptor chains by activated T lymphocytes virtually depleted of monocytes/macrophages, indicating that these effects do not necessarily require prior modification of monocyte/macrophage function by AGC10. Human lymphocytes stimulated with anti-CD3 or PHA also displayed a markedly decreased capacity to secrete IL-2 and IFN-gamma, suggesting that AGC10 affected at least Th1 cell functions. Cell viability in cultures containing or lacking AGC10 was comparable over a 72-h period, and neither CD25 expression by, nor the viability of, PHA-stimulated Jurkat cells was altered by AGC10, ruling out that the effects of AGC10 are due to cell killing. These results highlight down-regulatory effects on activated T lymphocytes exerted by a membrane molecule from a parasite causing a disease whose acute phase is accompanied by immunosuppression.
Kierszenbaum
F
F
Department of Microbiology, Michigan State University, East Lansing 48824, USA. kierszen@pilot.msu.edu
de Diego
J L
JL
Fresno
M
M
Sztein
M B
MB
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000494:pharmacology; D015800:Protozoan Proteins / Q000276:immunology* / Q000494:pharmacology; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013936:Thymidine; D014316:Tritium; D014349:Trypanosoma cruzi / Q000276:immunology*; D015854:Up-Regulation
D016207:Cytokines; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D015375:Receptors, Interleukin-2; D014316:Tritium; D013936:Thymidine