Invariant NKT and NKT-like lymphocytes: two different T cell subsets that are differentially affected by ageing

The expression on T lymphocytes of surface receptors that are characteristically expressed on NK cells has led to the definition of a T cell subset that has been termed Natural Killer T (NKT) cells. Thus NKT cells constitute a minor lymphocyte population that exhibits features of both T cells and NK cells. However, the term 'NKT cell' has been applied variably to cells that express a restricted T-cell receptor (TCR) that recognizes glycolipids (alpha-GalCer) presented by the MHC-like molecule CD1d and that express CD161, as well as populations of conventional CD8 T cells that show up-regulated expression of NK-cell markers. The CD1d restricted T cells have a semi-invariant TCR using the Valpha24Jalpha18 genes in humans (Valpha24Jalpha18 in mice) and are denominated invariant NKT (iNKT) cells. On the other hand mainstream T cells that express NK associated receptors (NKR) show a highly specialized effector memory phenotype and are frequently referred as NKT-like cells. These T lymphocyte subsets are differentially affected by ageing. Whereas human peripheral blood iNKT cells decrease with age, there is an increase in the percentage of peripheral blood NKT-like T lymphocytes.