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

gamma delta T cells producing interleukin-17A (gamma delta 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 gamma delta T17 via the expression of transforming growth factor-beta 1 (TGF beta 1). However, we have previously found that Th17 cells were not required for expansion of gamma delta 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 beta 1 to maintain gamma delta T17 cells in the lung and lymphoid tissues. At steady state, we found no defect in gamma delta T17 cells in the thymus or periphery of these mice. Further, STAT3-deficient CD4(+) T cells produced significantly higher levels of TGF beta 1 than wild-type CD4(+) T cells under Th17 differentiation conditions in vitro. To determine whether STAT3-deficient CD4(+) T cells could expand gamma delta T17 cells in vivo, we used TCR beta(-/ -) mice, which are known to have a defect in gamma delta 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 gamma delta T17 cells in TCR beta(-/-) mice. In contrast, interferon-gamma(+) gamma delta T cells preferentially expanded, particularly in the lungs. Interestingly, we found in vivo and in vitro that TGF beta 1 may negatively regulate the pool of gamma delta T17 cells. Our data suggest that Th17 cells and TGF beta 1 are not required for the maintenance of gamma delta T17 cells.