Tissue-specific segregation of CD1d-dependent and CD1d-independent NK T cells

NKT cells, defined as T cells expressing the NK cell marker NK1.1, are invo lved in tumor rejection and regulation of autoimmunity via the production o f cytokines. We show in this study that two types of NKT cells can be defin ed on the basis of their reactivity to the monomorphic MHC class I-like mol ecule CD1d, One type of NKT cell is positively selected by CD1d and express es a biased TCP repertoire together with a phenotype found on activated T c ells. A second type of NKT cell, in contrast, develops in the absence of CD 1d, and expresses a diverse TCR repertoire and a phenotype found on naive T cells and NK cells. Importantly, the two types of NKT cells segregate in d istinct tissues. Whereas thymus and liver contain primarily CD1d-dependent NKT cells, spleen and bone marrow are enriched in CD1d-independent NKT cell s. Collectively, our data suggest that recognition of tissue-specific ligan ds by the TCR controls localization and activation of NKT cells.