Interleukin-4-dependent innate collaboration between iNKT cells and B-1 B cells controls adaptative contact sensitivity.
We showed that hepatic Valpha14+ invariant natural killer T (iNKT) cells, via their rapid interleukin (IL)-4 production, activate B-1 cells to initiate contact sensitivity (CS). This innate collaboration was absent in IL-4(-/-) and signal transducer and activator of transcription (STAT)-6(-/-) mice and was inhibited by anti-IL-4 treatment. These mice have defective CS because they fail to locally recruit the sensitized effector T cells of acquired immunity. Their CS is reconstituted by transfer of downstream-acting 1-day immune B-1 cells from wild-type mice. Responses were not reconstituted with B-1 cells from IL-4 receptor-alpha(-/-) or STAT-6(-/-) mice, nor by IL-4 treatment of B cell-deficient mice at immunization. Finally, IL-4 was preferentially and transiently produced by hepatic iNKT cells within 7 min after sensitization to mediate collaboration between innate-like iNKT cells and the B-1 B cells that participate in the recruitment of effector T cells in vivo.
Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520-8013, USA.
Regis A
RA
Campos
Marian
M
Szczepanik
Atsuko
A
Itakura
Mariette
M
Lisbonne
Neelendu
N
Dey
Maria C
MC
Leite-de-Moraes
Philip W
PW
Askenase
D019264:Adoptive Transfer; D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D003877:Dermatitis, Contact / Q000209:etiology / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007108:Immune Tolerance / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010853:Picryl Chloride; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D019948:Receptors, Interleukin-4 / Q000276:immunology; D050800:STAT6 Transcription Factor / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019948:Receptors, Interleukin-4; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C045084:invariant chain; D015847:Interleukin-4; D010853:Picryl Chloride