title: TGF-beta regulates pathology but not tissue CD8+ T cell dysfunction during experimental Trypanosoma cruzi infection.
abstract: Infection with the protozoan parasite Trypanosoma cruzi leads to chronic infection, with parasite persistence primarily in muscle tissue. CD8(+) T cells isolated from muscle tissue of T. cruzi-infected mice display decreased production of IFN-gamma in response to T cell receptor engagement. The expression of TGF-beta at the site of CD8(+) T cell dysfunction and parasite persistence suggested that this immunoregulatory cytokine might play a role in these processes. Mice expressing a T cell-specific dominant negative TGF-beta receptor type II (DNRII) were therefore infected with T. cruzi. Infection of DNRII mice resulted in massive CD8(+) T cell proliferation, leading to increased numbers but decreased frequencies of antigen-specific CD8(+) T cells in the spleen compared to wild-type mice. However, TGF-beta unresponsiveness failed to restore effector functions of CD8(+) T cells isolated from muscle tissue. Histological examination of skeletal muscle from T. cruzi-infected DNRII mice revealed an extensive cellular infiltrate, and DNRII mice displayed higher susceptibility to infection. Overall, while TGF-beta does not appear to be responsible for CD8(+) T cell unresponsiveness in peripheral tissue in T. cruzi-infected mice, these data suggest a role for TGF-beta in control of immunopathology in response to T. cruzi infection.
authors.affiliation: Department of Cellular Biology and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30605, USA.
authors.forename: Diana L
authors.initials: DL
authors.lastname: Martin
authors.forename: Miriam
authors.initials: M
authors.lastname: Postan
authors.forename: Philip
authors.initials: P
authors.lastname: Lucas
authors.forename: Ronald
authors.initials: R
authors.lastname: Gress
authors.forename: Rick L
authors.initials: RL
authors.lastname: Tarleton
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002478:Cells, Cultured; D014355:Chagas Disease / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000502:physiology*