Early commitment of naïve 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 naïve 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 naïve 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 naïve CD4(+) T cells into a T(FH) cell fate, and thus underpin antibody-mediated immunity.
Ma
Cindy S
CS
Garvan Institute of Medical Research, NSW, Australia.
Suryani
Santi
S
Avery
Danielle T
DT
Chan
Anna
A
Nanan
Ralph
R
Santner-Nanan
Brigitte
B
Deenick
Elissa K
EK
Tangye
Stuart G
SG
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D018664:Interleukin-12 / Q000276:immunology*; D007378:Interleukins / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology*; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology*; D000098546:Interleukin-21
D007378:Interleukins; D018664:Interleukin-12; D000098546:Interleukin-21