Type II NKT cells facilitate Alum-sensing and humoral immunity.
Alum-based adjuvants facilitate vaccine-driven humoral immunity, but their mechanism of action remains poorly understood. Herein, we report that lack of type II NKT cells is associated with intact, mature B cells but dampened humoral immunity following immunization with Alum-adsorbed T-dependent antigen. Type II NKT cells facilitated production of IL-4, IL-5, IL-10, IL-13, and antibody by LN and splenocyte cultures following Alum/antigen administration in vivo and antigen restimulation in vitro. Addition of IL-4 and IL-5 to type II NKT-deficient cultures restored in vitro antibody production. Intracellular staining revealed that Alum-primed type II NKT cells coordinated IL-4 secretion by T cells. Alum did not significantly affect CD1d expression in vivo, but addition of CD1d-blocking mAb diminished cytokine production and in vitro antibody production. Type II NKT cells therefore function as part of the Alum-sensing apparatus and in a CD1d-dependent manner, facilitate T(H)2-driven humoral immunity. This may have important consequences for understanding the mechanism of action of Alum-containing vaccines.
Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Hemangi B
HB
Shah
T Scott
TS
Devera
Pragya
P
Rampuria
Gillian A
GA
Lang
Mark L
ML
Lang
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D055610:Antigens, CD1d / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D056724:Immunity, Humoral / Q000187:drug effects*; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D055611:Natural Killer T-Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D055610:Antigens, CD1d; D016207:Cytokines; D007074:Immunoglobulin G; C041524:aluminum sulfate