Tissue-specific segregation of TCRγ δ+ NKT cells according to phenotype TCR repertoire and activation status: parallels with TCR α β+NKT cells

Whereas the majority of NKT cells in the mouse express an alpha beta TCR (NKT alpha beta cells), a small subset of NKT cells express a gamma delta TCR (NKT gamma delta). Here we have systematically analyzed the phenotype, TCR repertoire and activation status of NKT gamma delta cells in the thymus, liver, spleen and bone marrow of normal C57BL/6 mice. Our data indicate that NKT gamma delta cells segregate in a tissue-specific manner according to these parameters. While most NKT gamma delta cells in the thymus and liver have a recently activated CD62L(lo) phenotype and a TCR repertoire that is heavily biased to V gamma1.1 and V delta6.3, the majority of NKT gamma delta cells in the spleen and bone marrow are CD62L(hi) and have a much less biased TCR repertoire. Moreover, expression of NK markers is high on NKT gamma delta cells in spleen and bone marrow but low in thymus and liver Collectively our results reveal a tissue-specific segregation of NKT gamma delta cells that is strikingly similar to that recently described for CD1d-dependent and Cd1d-independent NKT alpha beta cells. We therefore propose that chronic TCR activation by tissue-specific endogenous ligands is a generic property of NKT cells of both the alpha beta and gamma delta lineages.