| First Author | Rampuria P | Year | 2017 |
| Journal | J Leukoc Biol | Volume | 101 |
| Issue | 2 | Pages | 567-576 |
| PubMed ID | 27566831 | Mgi Jnum | J:243516 |
| Mgi Id | MGI:5908768 | Doi | 10.1189/jlb.4A0616-271R |
| Citation | Rampuria P, et al. (2017) Coordination between T helper cells, iNKT cells, and their follicular helper subsets in the humoral immune response against Clostridium difficile toxin B. J Leukoc Biol 101(2):567-576 |
| abstractText | Activation of iNKT cells with the CD1d-binding glycolipid adjuvant alpha-galactosylceramide (alpha-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 alpha-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 alpha-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 alpha-GC. Our results demonstrated that alpha-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. |
