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J Leukoc Biol. 2017 Feb;101(2):567-576. doi: 10.1189/jlb.4A0616-271R. Epub 2016 Aug 26.

Coordination between T helper cells, iNKT cells, and their follicular helper subsets in the humoral immune response against Clostridium difficile toxin B.

Author information

1
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
2
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA mark-lang@ouhsc.edu.

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.

KEYWORDS:

CD1d; T follicular helper; humoral immunity; iNKT follicular helper

PMID:
27566831
PMCID:
PMC5235901
DOI:
10.1189/jlb.4A0616-271R
[Indexed for MEDLINE]
Free PMC Article

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