Increased host resistance against Pneumocystis carinii pneumonia in γδ T-cell-deficient mice: Protective role of gamma interferon and CD8+ T cells

Academic Article

Abstract

  • Although a clear relationship between αβ T-cell receptor-positive αβ-TCR ) CD4 T cells and susceptibility to Pneumocystis carinii infection exists, the role of other T-cell subsets is less clearly defined. Previous studies have shown that γδ-TCR T cells infiltrate into the lung during P. carinii pneumonia. Therefore, the present study examined the role of γδ-TCR T cells in host defense against P. carinii pneumonia. C57BL/6 (control) and B6.129P2-Tcrd (γδ-TCR T-cell-deficient) mice were inoculated intratracheally with P. carinii. At specific time points, mice were sacrificed and analyzed for P. carinii burden, T-cell subsets, and cytokine levels in lung tissue. Analysis of P. carinii burden showed a more rapid and complete resolution of infection in γδ-TCR T-cell-deficient mice than in C57BL/6 controls. This augmented resolution was associated with elevated gamma interferon (IFN-γ) levels in bronchoalveolar lavage fluid predominantly produced by CD8 T cells, as well as an increased recruitment of CD8 T cells in general. In separate experiments, neutralization of IFN-γ or depletion of CD8 T cells early during infection abolished the augmented resolution previously observed in γδ-TCR T-cell-deficient mice. These results show that the presence of γδ-TCR T cells modulates host susceptibility to P. carinii pneumonia through interactions with pulmonary CD8 T cells and tissue production of IFN-γ. + + + + tmlMom + + + + + + + +
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    Digital Object Identifier (doi)

    Author List

  • Steele C; Zheng M; Young E; Marrero L; Shellito JE; Kolls JK
  • Start Page

  • 5208
  • End Page

  • 5215
  • Volume

  • 70
  • Issue

  • 9