title: TLR-dependent IL-4 production by invariant Valpha14+Jalpha18+ NKT cells to initiate contact sensitivity in vivo.
abstract: LPS stimulated B-1 cell polyclonal in vivo IgM responses depend on IL-4 release by invariant Valpha14+Jalpha18+ NKT (iNKT) cells. The IgM Abs can recruit effector T cells to mediate contact sensitivity. LPS activates the B-1 cell response just 1 day later, and depends on CD1d, iNKT cells, IL-4, TLR4, and MyD88. LPS in vivo and in vitro stimulates rapid preferential production of IL-4 in hepatic iNKT cells within 2 h. TLR4 were demonstrated in iNKT cells by flow cytometry and functional studies. Thus, innate microbial stimulation via TLR can activate iNKT cell and B-1 cell collaboration. The result is polyclonal IgM Ab responses capable of recruiting Ag-specific T cells into tissues. This may be involved in the promotion of autoimmunity by infectious agents.
authors.affiliation: Sections of Allergy and Clinical Immunology and Cardiology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA. philip.askenase@yale.edu
authors.forename: Philip W
authors.initials: PW
authors.lastname: Askenase
authors.forename: Atsuko
authors.initials: A
authors.lastname: Itakura
authors.forename: Maria C
authors.initials: MC
authors.lastname: Leite-de-Moraes
authors.forename: Mariette
authors.initials: M
authors.lastname: Lisbonne
authors.forename: Sukit
authors.initials: S
authors.lastname: Roongapinun
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Goldstein
authors.forename: Marian
authors.initials: M
authors.lastname: Szczepanik
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D001402:B-Lymphocytes / Q000276:immunology; D007113:Immunity, Innate; D007075:Immunoglobulin M / Q000096:biosynthesis; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008211:Lymphocyte Cooperation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D007075:Immunoglobulin M; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D015847:Interleukin-4