title: Human CD4+ invariant NKT cells are involved in antibacterial immunity against Brucella suis through CD1d-dependent but CD4-independent mechanisms.
abstract: Human invariant NKT (iNKT) cells are a unique subset of T cells, which recognize glycolipids presented by the CD1d. Among the iNKT cells, several functionally distinct subsets have been characterized according to CD4 and/or CD8 co-receptor expression. The current study is focussed on the CD4(+) iNKT cell subset and its role in an anti-infectious response. We have examined the role of CD4(+) iNKT cells on the intracellular Brucella suis growth. Our results indicate that CD4(+) iNKT cells impair the intramacrophagic growth of Brucella. This inhibition is due to a combination of soluble and contact-dependent mechanisms: IFN-gamma is weakly involved while cytotoxic activities such as the induction of the Fas pathway and the release of lytic granules are major mechanisms. The impairment of Brucella growth by CD4(+) iNKT cells requires an interaction with CD1d on macrophage surface. Also, we have shown that although CD4 regulates several biological responses of CD4(+) iNKT cells, it is not involved in their antibacterial activity. Here, we have shown for the first time that the CD4(+) iNKT cell population has antibacterial activity and thus, participates directly in the elimination of bacteria and/or in the control of bacterial growth by killing infected cells.
authors.affiliation: Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé, Université Montpellier 1, Montpellier, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Bessoles
authors.forename: Sherri
authors.initials: S
authors.lastname: Dudal
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Françoise
authors.initials: F
authors.lastname: Sanchez
authors.forename: Virginie
authors.initials: V
authors.lastname: Lafont
mesh_terms: D055610:Antigens, CD1d / Q000276:immunology*; D041021:Brucella suis / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology*; D015550:Cell Degranulation / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D055610:Antigens, CD1d; D015704:CD4 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C508598:IL4 protein, human; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D015847:Interleukin-4; D007371:Interferon-gamma