EVIDENCE FOR PROGRAMMED CELL-DEATH OF SELF-REACTIVE GAMMA-DELTA T-CELL RECEPTOR-POSITIVE THYMOCYTES

The negative selection of T cells expressing the gammadelta cell antigen receptor (gammadelta T cells) was studied using transgenic mice expressing a gammadelta receptor with specificity for an H-2T-linked class I major histocompatibility complex molecule from H-2b mice. The potentially self-reactive gammadelta thymocytes in H-2b/d transgenic mice are larger and have lower levels of gammadelta T cell receptor expression than gammadelta thymocytes from H-2d mice. H-2b/d gammadelta thymocytes do not respond to H-2b antigen-presenting cells, and thus are inactive compared to H-2d gammadelta thymocytes. However, the H-2bd gammadelta thymocyte population, but not the H-2d gammadelta thymocyte population, undergoes a high rate of programmed cell death when placed in overnight culture. These observations constitute the first direct evidence that self-reactive gammadelta thymocytes undergo programmed cell death. This in vitro programmed cell death of self-reactive gammadelta thymocytes may reflect the clonal deletion process that results in a depletion of gammadelta T cells in the peripheral lymphoid organs of adult H-2b/d mice. We also present evidence that self-reactive gammadelta T cells, similarly to alphabeta T cells, undergo a lesser degree of clonal deletion in neonatal mice compared to adult mice.