Early commitment of naive human CD4(+) T cells to the T follicular helper (T(FH)) cell lineage is induced by IL-12
T follicular helper (T(FH)) cells are a specialized subset of CD4(+) T cells that localize to B-cell follicles, where they are positioned to provide help for the induction of optimal humoral immune responses. Key features of T(FH) cells are the expressions of CXCR5, ICOS, interleukin (IL)-21 and BCL-6. The requirements for human T(FH) cell development are unknown. Here we show that IL-6, IL-12, IL-21 and IL-23 are capable of inducing IL-21 expression in naive CD4(+) T cells isolated from human tonsils, peripheral blood and cord blood. However, only IL-12 induced sustained expressions of CXCR5 and ICOS on these activated naive CD4(+) T cells, and endowed them with the ability to provide increased help to B cells for their differentiation into immunoglobulin-secreting cells. The effects of IL-12 were independent of interferon-gamma and T-bet, and associated with upregulation of BCL-6 expression. Thus, these cytokines, particularly IL-12, are likely to act at an early stage during dendritic cell-mediated priming of naive CD4(+) T cells into a T(FH) cell fate, and thus underpin antibody-mediated immunity.Immunology and Cell Biology advance online publication, 1 September 2009; doi:10.1038/icb.2009.64.
|Authors||Ma, C. S.; Suryani, S.; Avery, D. T.; Chan, A.; Nanan, R.; Santner-Nanan, B.; Deenick, E. K.; Tangye, S. G.|
|Responsible Garvan Author|
|Publisher Name||IMMUNOLOGY AND CELL BIOLOGY|
|DOI||icb200964 [pii] 10.1038/icb.2009.64|
|URL link to publisher's version||http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19721453|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10256|