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Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis.
- Source :
- Cell Reports; Mar2017, Vol. 18 Issue 13, p3091-3104, 14p
- Publication Year :
- 2017
-
Abstract
- 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<superscript>+</superscript>CXCR3<superscript>+</superscript>T-bet<superscript>dim</superscript> 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<superscript>+</superscript>KLRG1<superscript>+</superscript> Th1 cells that persists poorly and can neither migrate into the lung parenchyma nor control Mtb growth. Furthermore, T-bet suppresses development of CD69<superscript>+</superscript>CD103<superscript>+</superscript> tissue resident phenotype effectors in lung. In contrast, Th1-cell-derived IFN-γ inhibits the accumulation of intravascular CX3CR1<superscript>+</superscript>KLRG1<superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 26391856
- Volume :
- 18
- Issue :
- 13
- Database :
- Complementary Index
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- 122107741
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.03.007