Main content area

CD1d-unrestricted NKT cells are endowed with a hybrid function far superior than that of iNKT cells

Farr, Alexander R., Wu, Weisheng, Choi, Bongkum, Cavalcoli, James D., Laouar, Yasmina
Proceedings of the National Academy of Sciences of the United States of America 2014 v.111 no.35 pp. 12841-12846
T-lymphocytes, adaptive immunity, cytokines, cytotoxicity, natural killer cells
Invariant natural killer T (iNKT) cells to date represent the best example of cells known to have a hybrid function, representing both innate and adaptive immunity. Shared phenotypic similarities with NK cells together with a rapid response to a cytokine stimulus and a productive TCR engagement are the features that underline the hybrid nature of iNKT cells. Using these criteria, we provide molecular and functional evidence demonstrating that CD1d-independent (CD1d ⁱⁿᵈ) NKT cells, a population of CD1d-unrestricted NKT cells, are endowed with a hybrid function far superior to that of iNKT cells: (i) an extensive shared program with NK cells, (ii) a closer Euclidian distance with NK cells, and (iii) the ability to respond to innate stimuli (Poly:IC) with cytotoxic potential in the same manner as NK cells identify a hybrid feature in CD1d ⁱⁿᵈNKT cells that truly fulfills the dual function of an NK and a T cell. Our finding that CD1d ⁱⁿᵈNKT cells are programmed to act like NK cells in response to innate signals while being capable of adaptive responses is unprecedented, and thus might reemphasize CD1d-unrestricted NKT cells as a subset of lymphocytes that could affect biological processes of antimicrobial and tumor immunity in a unique way.