Trypanosoma cruzi: The Effect of Nitric Oxide Synthesis Inhibition on the CD4 T Cell Response to the trans-Sialidase Superfamily

Millar, A. E., and Kahn, S. J. 2000. Trypanosoma cruzi: The effect of nitric oxide synthesis inhibition on the CD4 T cell response to the trans-sialidase superfamily. Experimental Parasitology94, 84–91. During Trypanosoma cruzi infection the trans-sialidase superfamily stimulates the development of a large population of CD4 T lymphocytes that produces IFN;ZG. 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;xG-nitro-L-arginine methylester (L-NAME), an inhibitor of inducible nitric oxide synthase (iNOS), or N;xG-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 IFN;ZG, 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.