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In Vitro Differentiation of Naive CD4+ T Cells into Pathogenic Th17 Cells in Mouse
Published on: October 25, 2024
Regulatory effect of gammadelta T cells on IL-17+ uveitogenic T cells
Hong Nian1, Hui Shao, Guoming Zhang
1Doheny Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, California 90033, USA.
Purpose:
To characterize the regulatory effect of gammadelta T cells in the activation of IL-17+ uveitogenic T cells.
Methods:
The authors administered the gammadelta TCR-specific antibody GL3 to B6 mice before or after antigen immunization and examined Th1- or Th17-polarized T-cell responses. The intensity of Th17 responses was also examined in responder T cells containing varying numbers of gammadelta T cells.
Results:
GL3 treatment resulted in varying degrees of depletion of circulating gammadelta T cells, depending on when the antibody was administered. The intensity of the alphabetaTCR+IL-17+, but not the alphabetaTCR+IFN-gamma+, IRBP-specific T-cell responses was correlated to the percentage of gammadelta T cells in the responder T cells. Kinetic studies showed that early IL-17+ T cells were primarily gammadelta T cells, with a later gradual shift to alphabeta T cells. A close association was seen between the intensity of the IL-17+ autoreactive T-cell response and the percentage of gammadelta T cells in the responder T cells. Although a modest increase in gammadelta T cells among the responder T cells promoted the expansion of IL-17+ alphabetaTCR+ T cells, a higher proportion of gammadelta T cells inhibited it.
Conclusions:
gammadelta T cells are actively involved in the generation of alphabetaTCR+IL-17+ T cells. The number of gammadelta T cells and the alphabeta/gammadelta T-cell ratio in the responder T cells regulate the intensity of the Th17-type autoreactive T-cell response.
