In:
The Journal of Immunology, The American Association of Immunologists, Vol. 202, No. 1_Supplement ( 2019-05-01), p. 195.15-195.15
Abstract:
Treatment with glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonistic antibody (DTA-1) elicits potent antitumor immune responses in various tumor models. In this study, we demonstrate the crucial role of interleukin (IL)-21–producing follicular helper T (Tfh) cells in DTA-1-induced tumor inhibition. Administration of DTA-1 increased IL-21 expression from CD4 T cells, which is mainly made up of Tfh cells, in an antigen specific manner. Furthermore, mice treated with a neutralizing antibody to IL-21 receptor and Bcl6fl/flCD4cre mice exhibited abrogated antitumor activity induced by DTA-1. Mechanistically, IL-4 plays critical roles for the induction of IL-21–expressing Th cells by GITR co-stimulation, which is mediated by Bcl6 and c-Maf. Thus, our findings identify GITR co-stimulation as an inducer of IL-21–expressing Tfh cells and provide a novel mechanism for its antitumor activity.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.202.Supp.195.15
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2019
detail.hit.zdb_id:
1475085-5
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