Evidence for the divergence of innate and adaptive T-cell precursors before commitment to the alphabeta and gammadelta lineages.

摘要

In addition to adaptive T cells, the thymus supports the development of unconventional T cells such as natural killer T (NKT) and CD8alphaalpha intraepithelial lymphocytes (IELs), which have innate functional properties, particular antigenic specificities, and tissue localization. Both conventional and innate T cells are believed to develop from common precursors undergoing instructive, TCR-mediated lineage fate decisions, but innate T cells are proposed to undergo positive instead of negative selection in response to agonistic TCR signals. In the present study, we show that, in contrast to conventional alphabetaT cells, innate alphabetaT cells are not selected against functional TCRgamma rearrangements and express TCRgamma mRNA. Likewise, in contrast to the majority of gammadeltaT cells, thymic innate gammadeltaT cells are not efficiently selected against functional TCRbeta chains. In precursors of conventional T cells, autonomous TCR signals emanating from the pre-TCR or gammadeltaTCR in the absence of ligand mediate selection against the TCR of the opposite isotype and alphabeta/gammadelta lineage commitment. Our data suggest that developing innate T cells ignore such signals and rely solely on agonistic TCR interactions. Consistently, most innate T cells reacted strongly against autologous thymocytes. These results suggest that innate and adaptive T-cell lineages do not develop from the same pool of precursors and potentially diverge before alphabeta/gammadelta lineage commitment.