Nitric Oxide Limits the Expansion of Antigen-Specific T Cells in Mice Infected with the Microfilariae ofBrugia pahangi

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Abstract
Infection of BALB/c mice with the microfilariae (Mf) of the filarial nematodeBrugia pahangiresults in an antigen-specific proliferative defect that is induced by high levels of NO. Using carboxyfluorescein diacetate succinimydl ester and cell surface labeling, it was possible to identify a population of antigen-specific T cells from Mf-infected BALB/c mice that expressed particularly high levels of CD4 (CD4hi). These cells proliferated in culture only when inducible NO synthase was inhibited and accounted for almost all of the antigen-specific proliferative response under those conditions. CD4hicells also expressed high levels of CD44, consistent with their status as activated T cells. A similar population of CD4hicells was observed in cultures from Mf-infected gamma interferon receptor knockout (IFN-γR−/−) mice. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining revealed that the CD4+T cells from Mf-infected wild-type mice were preferentially susceptible to apoptosis compared to CD4+T cells from IFN-γR−/−mice. These studies suggest that the expansion of antigen-specific T cells in Mf-infected mice is limited by NO.

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