| First Author | Gern BH | Year | 2021 |
| Journal | Cell Host Microbe | Volume | 29 |
| Issue | 4 | Pages | 594-606.e6 |
| PubMed ID | 33711270 | Mgi Jnum | J:321373 |
| Mgi Id | MGI:6741200 | Doi | 10.1016/j.chom.2021.02.005 |
| Citation | Gern BH, et al. (2021) TGFbeta restricts expansion, survival, and function of T cells within the tuberculous granuloma. Cell Host Microbe 29(4):594-606.e6 |
| abstractText | CD4 T cell effector function is required for optimal containment of Mycobacterium tuberculosis (Mtb) infection. IFN produced by CD4 T cells is a key cytokine that contributes to protection. However, lung-infiltrating CD4 T cells have a limited ability to produce IFN, and IFN plays a lesser protective role within the lung than at sites of Mtb dissemination. In a murine infection model, we observed that IFN production by Mtb-specific CD4 T cells is rapidly extinguished within the granuloma but not within unaffected lung regions, suggesting localized immunosuppression. We identified a signature of TGFbeta signaling within granuloma-infiltrating T cells in both mice and rhesus macaques. Selective blockade of TGFbeta signaling in T cells resulted in an accumulation of terminally differentiated effector CD4 T cells, improved IFN production within granulomas, and reduced bacterial burdens. These findings uncover a spatially localized immunosuppressive mechanism associated with Mtb infection and provide potential targets for host-directed therapy. |
