| Abstrakt: |
Moderately virulent strains of Cryptococcusneoformans, 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. J. Leukoc. Biol.55: 35–42; 1994. |
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