Distinct Contributions of CD4 + and CD8 + T Cells to Pathogenesis of Trypanosoma brucei Infection in the Context of Gamma Interferon and Interleukin-10

Author:

Liu Gongguan1,Sun Donglei1,Wu Hui1,Zhang Mingshun12,Huan Haixia1,Xu Jinjun1,Zhang Xiquan3,Zhou Hong2,Shi Meiqing1

Affiliation:

1. Division of Immunology, Virginia-Maryland Regional College of Veterinary Medicine, University of Maryland, College Park, Maryland, USA

2. Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, China

3. Department of Animal Genetics, Breeding and Reproduction, South China Agricultural University, Guangzhou, China

Abstract

ABSTRACT 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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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