Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12.
T follicular helper (Tfh) cells help development of antibody responses via interleukin-21 (IL-21). Here we show that activated human dendritic cells (DCs) induced naive CD4(+) T cells to become IL-21-producing Tfh-like cells through IL-12. CD4(+) T cells primed with IL-12 induced B cells to produce immunoglobulins in a fashion dependent on IL-21 and inducible costimulator (ICOS), thus sharing fundamental characteristics with Tfh cells. The induction of Tfh-like cells by activated DCs was inhibited by neutralizing IL-12. IL-12 induced two different IL-21-producers: IL-21(+)IFN-gamma(+)T-bet(+) Th1 cells and IL-21(+)IFN-gamma(-)T-bet(-) non-Th1 cells, in a manner dependent on signal transducer and activator of transcription 4 (STAT4). IL-12 also regulated IL-21 secretion by memory CD4(+) T cells. Thus, IL-12 produced by activated DCs regulates antibody responses via developing IL-21-producing Tfh-like cells and inducing IL-21 secretion from memory CD4(+) T cells. These data suggest that the developmental pathway of Tfh cells differs between mice and humans, which have considerable implications for vaccine development.
Schmitt
Nathalie
N
Baylor Institute for Immunology Research, Baylor Research Institute, Dallas, TX 75204, USA.
Morita
Rimpei
R
Bourdery
Laure
L
Bentebibel
Salah Eddine
SE
Zurawski
Sandra M
SM
Banchereau
Jacques
J
Ueno
Hideki
H
D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D007378:Interleukins / Q000276:immunology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000276:immunology / Q000378:metabolism; D050797:STAT4 Transcription Factor / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D000098546:Interleukin-21
D016207:Cytokines; D007378:Interleukins; D034741:RNA, Small Interfering; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D018664:Interleukin-12; D000098546:Interleukin-21