Increased Host Resistance againstPneumocystis cariniiPneumonia in γδ T-Cell-Deficient Mice: Protective Role of Gamma Interferon and CD8⁺T Cells

Abstract

Although a clear relationship between ␣␤ T-cell receptor-positive (␣␤-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 ␥␦-TCR ؉ T cells infiltrate into the lung during P. carinii pneumonia. Therefore, the present study examined the role of ␥␦-TCR ؉ T cells in host defense against P. carinii pneumonia. C57BL/6 (control) and B6.129P2-Tcrd tm1Mom (␥␦-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 ␥␦-TCR ؉ T-cell-deficient mice than in C57BL/6 controls. This augmented resolution was associated with elevated gamma interferon (IFN-␥) 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-␥ or depletion of CD8 ؉ T cells early during infection abolished the augmented resolution previously observed in ␥␦-TCR ؉ T-cell-deficient mice. These results show that the presence of ␥␦-TCR ؉ T cells modulates host susceptibility to P. carinii pneumonia through interactions with pulmonary CD8

Colonization by Pneumocystis jirovecii and Its Role in Disease

“…Steele and colleagues demonstrated that ␥␦ T cells accumulate in the lungs of immunocompetent mice in response to Pneumocystis infection. Interestingly, in ␥␦ T cell-deficient mice, resolution of infection was improved and correlated with increased CD8 ϩ T cell recruitment and IFN-␥ production (278). These results suggest that one role of ␥␦ T cells may be to influence recruitment of CD8 ϩ T cells to the lungs and possibly modulate their inflammatory effect.…”

Cutting Edge: Roles of Toll-Like Receptor 4 and IL-23 in IL-17 Expression in Response toKlebsiella pneumoniaeInfection

“…Stimulated CD8 ϩ CD45RO ϩ T cells from human preparations have also been demonstrated to generate significant IL-17 mRNA (17). We next depleted CD4 ϩ , CD8 ϩ , or both T cell subsets in C57BL/6 mice with Ab GK1.5 or 2.43, respectively, which deplete over 97% of lung and splenic CD4 ϩ or CD8 ϩ T cells (18,19). CD4 ϩ depletion resulted in 45% reduction in measurable IL-17 in BAL fluid 24 h after K. pneumoniae challenge (Fig.…”

Regulatory T Cells Dampen Pulmonary Inflammation and Lung Injury in an Animal Model ofPneumocystisPneumonia

“…However, adoptive transfer of CD8 ϩ cells isolated from AdIFN-treated animals to generate Tc1 cells resulted in decreased organism burden in the lungs of Pneumocystis-infected SCID mice (13,36). Furthermore, ␥␦-TCR ϩ T cell-deficient mice have augmented clearance of Pneumocystis associated with increased IFN-␥ producing CD8 ϩ T cells (37), suggesting the Tc1 subset of CD8 ϩ T cells are involved in host defense against Pneumocystis. We show Pneumocystis-infected SCID mice reconstituted with CD4…”