Type II NKT cells facilitate Alum-sensing and humoral immunity

1.OUHSC, 940 Stanton L. Young Blvd., BMSB 1019, Oklahoma City, OK 73104, USA. .
Journal of leukocyte biology (Impact Factor: 4.29). 07/2012; 92(4):883-93. DOI: 10.1189/jlb.0412177
Source: PubMed


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.

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    • "These studies suggest that IL-4-producing myeloid cells such as eosinophils and basophils do not participate in alum adjuvanticity or Th2 responses. Recently, it has been reported that CD1d-deficient [both type-I and -II natural killer T (NKT) cell-deficient]-mice, but not Jα18-deficient (only type-I NKT cell-deficient)-mice exhibited reduced levels of antigen-specific IgG1 [39]. Type-II NKT cells appear to be required for alum-induced antigen-specific IgG1 responses in the regulation of IL-4-producing T cells. "
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