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The Journal of Immunology, 2005, 175: 2340-2348.
Copyright © 2005 by The American Association of Immunologists

The Role of ICOS in the CXCR5+ Follicular B Helper T Cell Maintenance In Vivo1

Hisaya Akiba2,*, Kazuyoshi Takeda*, Yuko Kojima{ddagger}, Yoshihiko Usui*,§, Norihiro Harada*,{dagger}, Tomohide Yamazaki*, Juan Ma*, Katsunari Tezuka, Hideo Yagita* and Ko Okumura*

* Department of Immunology and {dagger} Department of Respiratory Medicine, and {ddagger} Division of Biomedical Imaging Research, Juntendo University School of Medicine, Tokyo, Japan; § Department of Ophthalmology, Tokyo Medical University, Tokyo, Japan; and Central Pharmaceutical Research Institute, Japan Tobacco, Osaka, Japan

ICOS is a new member of the CD28 family of costimulatory molecules that is expressed on activated T cells. Its ligand B7RP-1 is constitutively expressed on B cells. Although the blockade of ICOS/B7RP-1 interaction inhibits T cell-dependent Ab production and germinal center formation, the mechanism remains unclear. We examined the contribution of ICOS/B7RP-1 to the generation of CXCR5+ follicular B helper T (TFH) cells in vivo, which preferentially migrate to the B cell zone where they provide cognate help to B cells. In the spleen, anti-B7RP-1 mAb-treated or ICOS-deficient mice showed substantially impaired development of CXCR5+ TFH cells and peanut agglutinin+ germinal center B cells in response to primary or secondary immunization with SRBC. Expression of CXCR5 on CD4+ T cells was associated with ICOS expression. Adoptive transfer experiments showed that the development of CXCR5+ TFH cells was enhanced by interaction with B cells, which was abrogated by anti-B7RP-1 mAb treatment. The development of CXCR5+ TFH cells in the lymph nodes was also inhibited by the anti-B7RP-1 mAb treatment. These results indicated that the ICOS/B7RP-1 interaction plays an essential role in the development of CXCR5+ TFH cells in vivo.




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