Coordinated control of immunity to muscle stage Trichinella spiralis by IL-10, regulatory T cells, and TGF-beta.
We previously demonstrated that IL-10 is critical in the control of acute inflammation during development of Trichinella spiralis in the muscle. In this study, we use gene-targeted knockout mice, adoptive transfer of specific T cell populations, and in vivo Ab treatments to determine the mechanisms by which inflammation is controlled and effector T cell responses are moderated during muscle infection. We report that CD4(+)CD25(-) effector T cells, rather than CD4(+)CD25(+) regulatory T cells, suppress inflammation by an IL-10-dependent mechanism that limits IFN-gamma production and local inducible NO synthase induction. Conversely, we show that depletion of regulatory T cells during infection results in exaggerated Th2 responses. Finally, we provide evidence that, in the absence of IL-10, TGF-beta participates in control of local inflammation in infected muscle and promotes parasite survival.
Beiting
Daniel P
DP
James A. Baker Institute for Animal Health, College of Vetermiary Medicine, Cornell University, Ithaca, NY 14853, USA.
Gagliardo
Lucille F
LF
Hesse
Matthias
M
Bliss
Susan K
SK
Meskill
Diana
D
Appleton
Judith A
JA
D000818:Animals; D016764:Cell Polarity; D002470:Cell Survival; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009220:Myositis / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D017160:Trichinella spiralis / Q000276:immunology*; D014235:Trichinellosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007371:Interferon-gamma