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
✍ Scribed by Felipe Kierszenbaum; Juana L. de Diego; Manuel Fresno; Marcelo B. Sztein
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 145 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
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, [ 3 H]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 § ) and CD122 (IL-2R g ) on the lymphocyte membrane and a marked decrease in the level of upregulation of the expression of surface CD132 (IL-2R + or + 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-+ , 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.