The role of CD4+ and CD8+ T cells in the protective inflammatory response to a pulmonary cryptococcal infection

G. B. Huffnagle, M. F. Lipscomb, J. A. Lovchik, K. A. Hoag, N. E. Street

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170 Scopus citations

Abstract

Moderately virulent strains of Cryptococcus neoformans, inoculated via the trachea, cause a pulmonary infection in BALB/c mice that was gradually resolved by T lymphocyte-dependent mechanisms. The current studies, using monoclonal antibodies to deplete T cell subsets, demonstrated that CD4+ and CD8+ T cells combined to mediate a prominent pulmonary inflammatory infiltrate that included lymphocytes, macrophages, neutrophils, and eosinophils. The inflammatory response peaked 2 weeks after infection and coincided with the beginning of gradual pulmonary clearance of the infection. CD4/CD8 double deficiency (4-8-) markedly reduced the influx of all cells into the lungs. A CD4 deficiency had a more profound effect on the total number of inflammatory cells recruited to the lungs than a CD8 deficiency. Depletion of either CD8+ or CD4+ T cells significantly decreased pulmonary macrophages and neutrophils, but only a CD4 deficiency prevented the influx of eosinophils. Recruitment of CD8+ T cells occurred independently of CD4+ T cells, but CD4+ T cell recruitment to the lungs was significantly reduced in CD8-deficient mice. Mitogen-stimulated infiltrating lung lymphocytes from infected 4+8+ mice secreted both T helper cell type 1 (Th1) [interferon-γ (IFN-γ) and interleukin-2 (IL-2)] and Th2 (IL-4, IL-5, and IL-10) cytokines. CD4 deficiency resulted in loss of T cells secreting IL-4, IL-5, and IL-10. However, residual CD8+ T cells still secreted IL-2 and IFN-γ. Lung T cells from CD8-deficient mice secreted similar levels of IL-4, IL-5, and IL-10 on a per lung basis compared with 4+8+ mice despite decreased numbers of CD4+ T cells, but secreted reduced levels of IFN-γ. These experiments indicate that (1) CD4+ T cells play a dominant role in recruiting macrophages and granulocytes to the lung and (2) CD8+ T cells also mediate cellular recruitment, increase the magnitude of CD4+ T cell numbers in the infiltrate, and contribute to the local secretion of IFN-γ. Thus, these studies demonstrate that CD8+ T cells can independently mediate an inflammatory response to a large, particulate, extracellular antigen, a role heretofore attributed almost solely to CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)35-42
Number of pages8
JournalJournal of Leukocyte Biology
Volume55
Issue number1
Publication statusPublished - 1994

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Keywords

  • cytokines
  • pulmonary cryptococcosis
  • T lymphocytes

ASJC Scopus subject areas

  • Cell Biology

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