Freshly isolated Vα24+ CD4+ invariant natural killer T cells activated by α-galactosylceramide-pulsed B cells promote both IgG and IgE production

Abstract

CD1d-restricted invariant natural killer T (iNK T) cells activated by their experimental ligand α-galactosylceramide (α-GC) can produce both T helper 1 (Th1) and Th2 cytokines and display regulatory functions. Recent studies identified CD4+ and CD4- CD8- double-negative (DN) iNK T cells as the two major components of the human population and suggest that they display a Th2 and a Th1 profile, respectively. We compared the Th2-promoting activity of freshly isolated human CD4+ and DN iNK T cells in terms of their capacity to induce Ig production by autologous B cells. Secretion of IgG and IgE but not IgM was enhanced by the CD4+ T cell subset (including iNK T cells) but not by its DN counterpart. iNK T cells were directly responsible for this pro-Th2 effect, as demonstrated by the requirement for both α-GC stimulation and CD1d presentation, as well as by its disappearance upon iNK T cell depletion. Interaction with iNK T cells led to progressive accumulation of isotype-switched and activated B cells. Myeloid dendritic cells (DC) completely block the induction of Ig production in co-culture. This dominant inhibitory effect of myeloid DC was concomitant with a specific loss of interleukin (IL)-4 production by CD4+ iNK T but not by conventional T cells. These data support the conclusion that, conversely to the interferon (IFN)-γ-producing DN human iNK T cell population, interleukin (IL)-4-producing CD4+ iNK T cells can activate and help B cells to produce both IgG and IgE through a CD1d-dependent mechanism, in keeping with a functional Th1/Th2 dichotomy between these subsets. © 2007 The Author(s).