V alpha 14+ NK T cells: a novel lymphoid cell lineage with regulatory function

A novel lymphoid lineage, NK T cells, was recently found. The NK T cells are the major population in the periphery comprising 5% of splenic T cells and 40% of bone marrow T cells. They express a unique TCR composed of invariant V alpha 14J alpha 281 and V beta 8.2 together with NK receptor (NKRPI). Surprisingly, the invariant V alpha 14+ TCR is exclusively expressed on NK T cells but not on conventional T cells. As the selective decrease in V alpha 14+ NK T cell population in the periphery is tightly correlated with autoimmune disease development, V alpha 14+ NK T cells control development of autoimmune diseases. We also found that V alpha 14 TCR gene rearrangement and transcripts were detected at an early embryogenesis (d9.5) before the thymus formation. Therefore NK T cells are in the distinct category from conventional T cells. The target of NK T cells is found to be CD1 (class 1b, monomorphic class I MHC-like molecule) present on bone marrow-derived cells and is killed by Fas-FasL interaction or perforin-mediated mechanisms. These results indicate that NK T cells consist of an immunoregulatory system different from defense system in terms of homogeneous repertoire, extrathymic development in early stage of gestation, and their regulatory functional role.