TY - JOUR
T1 - Human Dendritic Cells Induce the Differentiation of Interleukin-21-Producing T Follicular Helper-like Cells through Interleukin-12
AU - Schmitt, Nathalie
AU - Morita, Rimpei
AU - Bourdery, Laure
AU - Bentebibel, Salah Eddine
AU - Zurawski, Sandra M.
AU - Banchereau, Jacques
AU - Ueno, Hideki
N1 - Funding Information:
We thank E. Kowalski and S. Coquery for cell sorting; L. Walters for cell processing from apheresis blood; G. Zurawski for IL-21 generation; and G. Xia and J. Connolly for technical discussion. This study was supported by U19-AI057234, R01-CA84512, R01-CA078846 (J.B.), and Baylor Health Care Foundation (H.U. and J.B.). J.B. holds the W.W. Caruth, Jr., Chair for Transplantation Immunology Research.
PY - 2009/7/17
Y1 - 2009/7/17
N2 - 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-γ+T-bet+ Th1 cells and IL-21+IFN-γ-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.
AB - 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-γ+T-bet+ Th1 cells and IL-21+IFN-γ-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.
KW - CELLIMMUNO
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U2 - 10.1016/j.immuni.2009.04.016
DO - 10.1016/j.immuni.2009.04.016
M3 - Article
C2 - 19592276
AN - SCOPUS:68249158536
VL - 31
SP - 158
EP - 169
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 1
ER -