title: Freshly isolated Valpha24+ CD4+ invariant natural killer T cells activated by alpha-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 alpha-galactosylceramide (alpha-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 alpha-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)-gamma-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.
authors.affiliation: Laboratoire d'Immunologie-Immunopathologie, Centre Hospitalier Universitaire La Milétrie, Pôle Biologie Santé Poitiers, France.
authors.forename: A
authors.initials: A
authors.lastname: Rossignol
authors.forename: A
authors.initials: A
authors.lastname: Barra
authors.forename: A
authors.initials: A
authors.lastname: Herbelin
authors.forename: J-L
authors.initials: JL
authors.lastname: Preud'homme
authors.forename: J-M
authors.initials: JM
authors.lastname: Gombert
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D018920:Coculture Techniques; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D005699:Galactosylceramides / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D016207:Cytokines; D005699:Galactosylceramides; D007074:Immunoglobulin G; D016693:Receptors, Antigen, T-Cell, alpha-beta; C493154:alpha-galactosylceramide; D007073:Immunoglobulin E