| First Author | Barber DL | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 3 | Pages | 1598-607 |
| PubMed ID | 21172867 | Mgi Jnum | J:168927 |
| Mgi Id | MGI:4939310 | Doi | 10.4049/jimmunol.1003304 |
| Citation | Barber DL, et al. (2011) CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition. J Immunol 186(3):1598-607 |
| abstractText | Although CD4 T cells are required for host resistance to Mycobacterium tuberculosis, they may also contribute to pathology. In this study, we examine the role of the inhibitory receptor PD-1 and its ligand PD-L1 during M. tuberculosis infection. After aerosol exposure, PD-1 knockout (KO) mice develop high numbers of M. tuberculosis-specific CD4 T cells but display markedly increased susceptibility to infection. Importantly, we show that CD4 T cells themselves drive the increased bacterial loads and pathology seen in infected PD-1 KO mice, and PD-1 deficiency in CD4 T cells is sufficient to trigger early mortality. PD-L1 KO mice also display enhanced albeit less severe susceptibility, indicating that T cells are regulated by multiple PD ligands during M. tuberculosis infection. M. tuberculosis-specific CD8 T cell responses were normal in PD-1 KO mice, and CD8 T cells only had a minor contribution to the exacerbated disease in the M. tuberculosis-infected PD-1 KO and PD-L1 KO mice. Thus, in the absence of the PD-1 pathway, M. tuberculosis benefits from CD4 T cell responses, and host resistance requires inhibition by PD-1 to prevent T cell-driven exacerbation of the infection. |
