Th17 cells are not required for maintenance of IL-17A-producing ?? T cells in vivo.

ABSTRACT: ?? T cells producing interleukin-17A (??T17) are thought to develop spontaneously in the thymus and to be maintained in the periphery. Previous studies suggested a role for T-helper 17 (Th17) cells in the maintenance of ??T17 via the expression of transforming growth factor-?1 (TGF?1). However, we have previously found that Th17 cells were not required for expansion of ??T17 cells after lung transplant in a mouse model. Using mice deficient in signal transducer and activator of transcription 3 (STAT3) in CD4+ T cells, which are unable to develop Th17 cells, we investigated the requirement for Th17 cells and TGF?1 to maintain ??T17 cells in the lung and lymphoid tissues. At steady state, we found no defect in ??T17 cells in the thymus or periphery of these mice. Further, STAT3-deficient CD4+ T cells produced significantly higher levels of TGF?1 than wild-type CD4+ T cells under Th17 differentiation conditions in vitro. To determine whether STAT3-deficient CD4+ T cells could expand ??T17 cells in vivo, we used TCR?-/- mice, which are known to have a defect in ??T17 cells that can be rescued by Th17 cells. However, adoptive transfer of wild-type Th17 cells or bulk CD4+ T cells did not expand ??T17 cells in TCR?-/- mice. In contrast, interferon-?+ ?? T cells preferentially expanded, particularly in the lungs. Interestingly, we found in vivo and in vitro that TGF?1 may negatively regulate the pool of ??T17 cells. Our data suggest that Th17 cells and TGF?1 are not required for the maintenance of ??T17 cells.

SUBMITTER: Gupta PK 

PROVIDER: S-EPMC5360492 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature