T-cell responses during Trypanosoma brucei infections in mice deficient ininducible nitric oxide synthase

We have investigated the possibility that nitric oxide (NO) synthesis may a ffect the course of a trypanosome infection via T-cell responses using mice deficient in inducible NO synthase (iNOS). Parasitemia levels increased at the same rate in both iNOS-deficient homozygous and control heterozygous m ice, and peak parasitemia values were the same in both groups. However, the heterozygous mice maintained higher parasitemia levels after the peak of a n infection than the homozygous mice due to a decrease in the rate of clear ance of parasites. In iNOS-deficient mice there was an increase in the numb ers of total CD4(+) cells and activated (interleukin-2 receptor-expressing) CD4(+) cells in infected mice compared with the numbers in uninfected mice . Spleen cells from infected iNOS-deficient mice displayed increased prolif erative responses and gamma interferon secretion when stimulated in vitro t han those of control mice. These data suggest that NO production depresses T-helper 1-like responses generated during Trypanosoma brucei infections, t hus promoting the survival of the parasite.