Distinct Contributions of CD4+ and CD8+ T Cells to Pathogenesis of Trypanosoma brucei Infection in the Context of Gamma Interferon and Interleukin-10.
Although gamma interferon (IFN-γ) and interleukin-10 (IL-10) have been shown to be critically involved in the pathogenesis of African trypanosomiasis, the contributions to this disease of CD4(+) and CD8(+) T cells, the major potential producers of the two cytokines, are incompletely understood. Here we show that, in contrast to previous findings, IFN-γ was produced by CD4(+), but not CD8(+), T cells in mice infected with Trypanosoma brucei. Without any impairment in the secretion of IFN-γ, infected CD8(-/-) mice survived significantly longer than infected wild-type mice, suggesting that CD8(+) T cells mediated mortality in an IFN-γ-independent manner. The increased survival of infected CD8(-/-) mice was significantly reduced in the absence of IL-10 signaling. Interestingly, IL-10 was also secreted mainly by CD4(+) T cells. Strikingly, depletion of CD4(+) T cells abrogated the prolonged survival of infected CD8(-/-) mice, demonstrating that CD4(+) T cells mediated protection. Infected wild-type mice and CD8(-/-) mice depleted of CD4(+) T cells had equal survival times, suggesting that the protection mediated by CD4(+) T cells was counteracted by the detrimental effects of CD8(+) T cells in infected wild-type mice. Interestingly, CD4(+) T cells also mediated the mortality of infected mice in the absence of IL-10 signaling, probably via excessive secretion of IFN-γ. Finally, CD4(+), but not CD8(+), T cells were critically involved in the synthesis of IgG antibodies during T. brucei infections. Collectively, these results highlight distinct roles of CD4(+) and CD8(+) T cells in the context of IFN-γ and IL-10 during T. brucei infections.
Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
Gongguan
G
Liu
Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
Donglei
D
Sun
Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
Hui
H
Wu
Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China.
Mingshun
M
Zhang
Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
Haixia
H
Huan
Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA.
Jinjun
J
Xu
Department of Animal Genetics, Breeding and Reproduction, South China Agricultural University, Guangzhou, China.
Xiquan
X
Zhang
Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China.
Hong
H
Zhou
Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA mshi@umd.edu.
Meiqing
M
Shi
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016019:Survival Analysis; D013997:Time Factors; D014346:Trypanosoma brucei brucei / Q000502:physiology*; D014353:Trypanosomiasis, African / Q000276:immunology* / Q000473:pathology*
D016753:Interleukin-10; D007371:Interferon-gamma