T-Cell responses during Trypanosoma brucei infections in mice deficient in inducible nitric oxide synthase.
We have investigated the possibility that nitric oxide (NO) synthesis may affect 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 mice, and peak parasitemia values were the same in both groups. However, the heterozygous mice maintained higher parasitemia levels after the peak of an infection than the homozygous mice due to a decrease in the rate of clearance of parasites. In iNOS-deficient mice there was an increase in the numbers 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 proliferative responses and gamma interferon secretion when stimulated in vitro than those of control mice. These data suggest that NO production depresses T-helper 1-like responses generated during Trypanosoma brucei infections, thus promoting the survival of the parasite.
Millar
A E
AE
Division of Infection & Immunity, I.B.L.S., University of Glasgow, Glasgow G12 8QQ, United Kingdom.
Sternberg
J
J
McSharry
C
C
Wei
X Q
XQ
Liew
F Y
FY
Turner
C M
CM
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000172:deficiency / Q000235:genetics* / Q000276:immunology*; D052247:Nitric Oxide Synthase Type II; D013601:T-Lymphocytes / Q000276:immunology*; D014346:Trypanosoma brucei brucei; D014353:Trypanosomiasis, African / Q000235:genetics / Q000276:immunology*
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse