+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12

Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12

Immunity 31(1): 158-169

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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 053607308

Download citation: RISBibTeXText

PMID: 19592276

DOI: 10.1016/j.immuni.2009.04.016

Related references

BCG stimulated dendritic cells induce an interleukin-10 producing T-cell population with no T helper 1 or T helper 2 bias in vitro. Immunology 121(2): 276-282, 2007

CD8+ immunoregulatory cells in the graft-versus-host reaction: CD8 T cells activate dendritic cells to secrete interleukin-12/interleukin-18 and induce T helper 1 autoantibody. Immunology 109(4): 476-486, 2003

Freshly isolated Peyer's patch, but not spleen, dendritic cells produce interleukin 10 and induce the differentiation of T helper type 2 cells. Journal of Experimental Medicine 190(2): 229-239, 1999

Interleukin-3 and interferon beta cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties. Blood 99(3): 993-998, 2002

TSLP-activated dendritic cells induce human T follicular helper cell differentiation through OX40-ligand. Journal of Experimental Medicine 214(5): 1529-1546, 2017

Human follicular dendritic cells and vascular cells produce interleukin-7: a potential role for interleukin-7 in the germinal center reaction. European Journal of Immunology 26(10): 2541-2544, 1996

CD40-deficient dendritic cells producing interleukin-10, but not interleukin-12, induce T-cell hyporesponsiveness in vitro and prevent acute allograft rejection. Immunology 98(2): 159-170, 1999

Bile acids induce monocyte differentiation toward interleukin-12 hypo-producing dendritic cells via a TGR5-dependent pathway. Immunology 136(2): 153-162, 2012

The Interleukin-2-mTORc1 Kinase Axis Defines the Signaling, Differentiation, and Metabolism of T Helper 1 and Follicular B Helper T Cells. Immunity 43(4): 690-702, 2015

Increased interleukin 21 and follicular helper T-like cells and reduced interleukin 10+ B cells in patients with new-onset systemic lupus erythematosus. Journal of Rheumatology 41(9): 1781-1792, 2014

Interleukin-3 modifies the capacity of human monocyte-derived dendritic cells to induce helper T cell responses Shift towards a TH2 cytokine secretion pattern. Journal of Investigative Dermatology 117(4): 1023, 2001

Dendritic cells induce interleukin-4 producing T cells from non-small cell lung cancer patients. Proceedings of the American Association for Cancer Research Annual Meeting 43: 97, 2002

Role of B7 signaling in the differentiation of naive CD4+ T cells to effector interleukin-4-producing T helper cells. Immunologic Research 14(3): 176-188, 1995

Interleukin 2-mediated conversion of ovarian cancer-associated CD4+ regulatory T cells into proinflammatory interleukin 17-producing helper T cells. Journal of ImmunoTherapy 32(2): 101-108, 2009

Interleukin 21 Is a T Helper (Th) Cell 2 Cytokine that Specifically Inhibits the Differentiation of Naive Th Cells into Interferon -producing Th1 Cells. Journal of Experimental Medicine 196(7): 969-977, 2002