CD8 T cells modulate CD4 T-cell and eosinophil-mediated pulmonary pathology in pneumocystis pneumonia in B-cell-deficient mice

Am J Pathol. 2006 Feb;168(2):466-75. doi: 10.2353/ajpath.2006.050724.


Pneumocystis spp. pneumonia (PCP) in humans and in surrogate animal species typically occurs in the absence of CD4 T cells, as takes place during acquired immune deficiency syndrome. However, patients treated with highly active anti-retroviral therapy sometimes exhibit an exacerbation of diseases such as PCP that coincides with resurgent CD4 T cells, a phenomenon known as immune reconstitution disease. We used an animal model of PCP using the B-cell-deficient muMT mouse together with antibody-mediated depletion of various T-cell subsets to examine the role of CD4 and CD8 T cells in the development of pathology in PCP. Although overt pathology occurs in the presence of CD4 T cells only, CD8 T cells only, or both, pulmonary injury occurs via different paths, depending on the complement of T cells present. Surprisingly, profound damage occurred when only CD4 T cells were present, and this pathology coincided with enhanced recruitment and activation of eosinophils and strong type 2 cytokine polarization in the alveolar environment. In addition, CD8 T cells can act to moderate this CD4 T cell-mediated pathology, possibly by increasing the ratio of putative CD25+ suppressor CD4 T cells to CD25- effector CD4 T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Bronchoalveolar Lavage
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / physiology*
  • Eosinophils / immunology*
  • Flow Cytometry
  • Lung / pathology
  • Lymphocyte Depletion
  • Mice
  • Mice, Inbred C57BL
  • Pneumonia, Pneumocystis / pathology*
  • Pulmonary Alveoli / immunology
  • Pulmonary Alveoli / microbiology
  • Pulmonary Alveoli / pathology