title: CD1d-unrestricted NKT cells are endowed with a hybrid function far superior than that of iNKT cells.
abstract: 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(ind)NKT cells that truly fulfills the dual function of an NK and a T cell. Our finding that CD1d(ind)NKT 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.
authors.affiliation: Departments of Microbiology and Immunology and.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Farr
authors.affiliation: Computational Medicine and Bioinformatics, University of Michigan School of Medicine, Ann Arbor, MI 48109.
authors.forename: Weisheng
authors.initials: W
authors.lastname: Wu
authors.affiliation: Departments of Microbiology and Immunology and.
authors.forename: Bongkum
authors.initials: B
authors.lastname: Choi
authors.affiliation: Computational Medicine and Bioinformatics, University of Michigan School of Medicine, Ann Arbor, MI 48109.
authors.forename: James D
authors.initials: JD
authors.lastname: Cavalcoli
authors.affiliation: Departments of Microbiology and Immunology and ylaouar@umich.edu.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Laouar
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology; D005260:Female; D023281:Genomics; D053804:Granzymes / Q000276:immunology; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology*
chemical_list: D055610:Antigens, CD1d; C584692:CD1d antigen, mouse; D053804:Granzymes; C509214:Gzmb protein, mouse
keywords: CD1d; MHC; NK receptors; granzyme B