Coordination between T helper cells, iNKT cells, and their follicular helper subsets in the humoral immune response against Clostridium difficile toxin B. Issue 2 (26th August 2016)

• Record Type: Journal Article
• Authors: Rampuria, Pragya; Lang, Gillian A; Devera, T Scott; Gilmore, Casey; Ballard, Jimmy D; Lang, Mark L
• Is Part Of: Journal of leukocyte biology. Volume 101:Issue 2(2017)
• Page Start: 567
• Page End: 576
• Publication Date: 2016-08-26
• Subjects: humoral immunity -- CD1d -- T follicular helper -- iNKT follicular helper; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.4A0616-271R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: Activation of iNKT cells with the CD1d-binding glycolipid adjuvant α-galactosylceramide (α-GC) enhances humoral immunity specific for coadministered T-dependent Ag. However, the relationship between the iNKT cell and the classic T helper (Th) or T follicular helper (Tfh) function following this immunization modality remains unclear. We show that immunization with the C-terminal domain (CTD) of Clostridium difficile toxin B (TcdB), accompanied by activation of iNKT cells with α-GC, led to enhanced production of CTD-specific IgG, which was CD1d- and iNKT cell-dependent and associated with increased neutralization of active TcdB. Immunization with CTD plus α-GC followed by NP hapten-linked CTD increased NP-specific IgG1 titers in an NKT-dependent manner, suggesting that iNKT activation could enhance Th or Tfh function or that iNKT and iNKTfh cells could provide supplemental, yet independent, B cell help. Th, Tfh, iNKT, and iNKTfh cells were, therefore, examined quantitatively, phenotypically, and functionally following immunization with CTD or with CTD plus α-GC. Our results demonstrated that α-GC–activated iNKT cells had no direct effect on the numbers, phenotype, or function of Th or Tfh cells. However, CD4 + T cell–specific ablation of the Bcl6 transcription factor demonstrated that Tfh and iNKTfh cells both contributed to B cell help. This work extends our understanding of the immune response to vaccination and demonstrates an important contribution by NKTfh cells to humoral immunity.