Th1 Differentiation Drives the Accumulation of Intravascular, Non-protective CD4 T Cells during Tuberculosis

作者：Michelle A. Sallin, Shunsuke Sakai, Keith D. Kauffman, Howard A. Young, Jinfang Zhu, Daniel L. Barber · 发表于：Cell Reports · 年份：2017 · DOI：10.1016/j.celrep.2017.03.007 · 被引用次数：123 · 研究领域：Tuberculosis Research and Epidemiology、Immune Cell Function and Interaction、Immune Response and Inflammation

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-γ 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.