Trypanosoma cruzi: the effect of nitric oxide synthesis inhibition on the CD4 T cell response to the trans-sialidase superfamily.
During Trypanosoma cruzi infection the trans-sialidase superfamily stimulates the development of a large population of CD4 T lymphocytes that produces IFNgamma. These CD4 T cells fail to proliferate when stimulated in vitro. Why they fail to proliferate remains unclear. Nitric oxide is a critical component of the host immune response against T. cruzi, and to determine if NO inhibits trans-sialidase superfamily-specific proliferative responses, mice were fed either N(G)-nitro-L-arginine methylester (L-NAME), an inhibitor of inducible nitric oxide synthase (iNOS), or N(G)-nitro-D-arginine methyl ester (D-NAME), an inactive analog of L-NAME. The L-NAME-fed mice had increased parasitemia and mortality compared to the D-NAME-fed mice. Following stimulation with a T. cruzi trans-sialidase superfamily protein, splenocytes from both groups of mice failed to proliferate but continued to make similar amounts of IFNgamma, suggesting that the development of the trans-sialidase superfamily-specific CD4 response was not affected by iNOS inhibition. In addition, IL-2 receptor (IL-2R) expression was increased on T cells isolated from L-NAME-fed mice. These data suggest that during T. cruzi infection NO causes downregulation of IL-2R expression, but does not cause inhibition of trans-sialidase superfamily-specific CD4 T cell proliferation. Rather, the trans-sialidase superfamily proliferation may be inhibited by epitope variation.
Millar
A E
AE
Departments of Pediatrics and Pathobiology, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA.
Kahn
S J
SJ
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D014355:Chagas Disease / Q000201:enzymology / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D015800:Protozoan Proteins / Q000276:immunology* / Q000494:pharmacology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology*
D000953:Antigens, Protozoan; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C096427:SA85 1.1 antigen, Trypanosoma cruzi; D009569:Nitric Oxide; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester