| First Author | Sallin MA | Year | 2017 |
| Journal | Cell Rep | Volume | 18 |
| Issue | 13 | Pages | 3091-3104 |
| PubMed ID | 28355562 | Mgi Jnum | J:254412 |
| Mgi Id | MGI:6103487 | Doi | 10.1016/j.celrep.2017.03.007 |
| Citation | Sallin MA, et al. (2017) Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis. Cell Rep 18(13):3091-3104 |
| abstractText | Recent data indicate that the differentiation state of Th1 cells determines their protective capacity against tuberculosis. Therefore, we examined the role of Th1-polarizing factors in the generation of protective and non-protective subsets of Mtb-specific Th1 cells. We find that IL-12/23p40 promotes Th1 cell expansion and maturation beyond the CD73(+)CXCR3(+)T-bet(dim) stage, and T-bet prevents deviation of Th1 cells into Th17 cells. Nevertheless, IL- 12/23p40 and T-bet are also essential for the production of a prominent subset of intravascular CX3CR1(+)KLRG1(+) Th1 cells that persists poorly and can neither migrate into the lung parenchyma nor control Mtb growth. Furthermore, T-bet suppresses development of CD69(+)CD103(+) tissue resident phenotype effectors in lung. In contrast, Th1-cell-derived IFN-gamma inhibits the accumulation of intravascular CX3CR1(+)KLRG1(+) Th1 cells. Thus, although IL-12 and T-bet are essential host survival factors, they simultaneously oppose lung CD4 T cell responses at several levels, demonstrating the dual nature of Th1 polarization in tuberculosis. |
