αβ Lineage‐committed thymocytes can be rescued by the γδ T cell receptor (TCR) in the absence of TCR β chain

Abstract

Commitment of the αβ and γδ T cell lineages within the thymus has been studied in T cell receptor (TCR)‐transgenic and TCR mutant murine strains. TCRγδ‐transgenic or TCRβ knockout mice, both of which are unable to generate TCRαβ‐positive T cells, develop phenotypically αβ‐like thymocytes in significant proportions. We provide evidence that in the absence of functional TCRβ protein, the γδTCR can promote the development of αβ‐like thymocytes, which, however, do not expand significantly and do not mature into γδ T cells. These results show that commitment to the αβ lineage can be determined independently of the isotype of the TCR, and suggest that αβ versus γδ T cell lineage commitment is principally regulated by mechanisms distinct from TCR‐mediated selection. To accommodate our data and those reported previously on the effect of TCRγ and δ gene rearrangements on αβ T cell development, we propose a model in which lineage commitment occurs independently of TCR gene rearrangement.