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-γ isweakly 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. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.