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Coordination between T helper cells, iNKT cells, and their follicular helper subsets in the humoral immune response against Clostridium difficile toxin B
Author(s) -
Rampuria Pragya,
Lang Gillian A.,
Devera T. Scott,
Gilmore Casey,
Ballard Jimmy D.,
Lang Mark L.
Publication year - 2017
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.4a0616-271r
Subject(s) - biology , clostridium difficile , clostridium difficile toxin a , immune system , immunology , toxin , microbiology and biotechnology , humoral immunity , t helper cell , t cell , antibiotics
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.