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

• Published in: The Journal of immunology (1950) 2005-08, Vol.175 (4), p.2340-2348
• Main Authors: Akiba, Hisaya, Takeda, Kazuyoshi, Kojima, Yuko, Usui, Yoshihiko, Harada, Norihiro, Yamazaki, Tomohide, Ma, Juan, Tezuka, Katsunari, Yagita, Hideo, Okumura, Ko
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - pharmacology; Antigens, Differentiation, T-Lymphocyte - biosynthesis; Antigens, Differentiation, T-Lymphocyte - genetics; Antigens, Differentiation, T-Lymphocyte - physiology; Antigens, Surface - biosynthesis; Antigens, Surface - genetics; B-Lymphocyte Subsets - cytology; B-Lymphocyte Subsets - immunology; B7-1 Antigen - immunology; CD28 Antigens - genetics; CD28 Antigens - physiology; CD40 Antigens - genetics; CD40 Antigens - physiology; Cell Differentiation - genetics; Cell Differentiation - immunology; Chemokines, CXC - metabolism; Female; Germinal Center - cytology; Germinal Center - immunology; Immunization, Secondary; Inducible T-Cell Co-Stimulator Ligand; Inducible T-Cell Co-Stimulator Protein; Membrane Glycoproteins - immunology; Membrane Proteins - biosynthesis; Membrane Proteins - deficiency; Membrane Proteins - genetics; Mice; Mice, Inbred A; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Mice, Knockout; Mice, SCID; Receptors, Chemokine - biosynthesis; Receptors, CXCR5; Receptors, Cytokine - biosynthesis; Receptors, OX40; Receptors, Tumor Necrosis Factor - biosynthesis; Receptors, Tumor Necrosis Factor - deficiency; Receptors, Tumor Necrosis Factor - genetics; Spleen - cytology; Spleen - immunology; Spleen - metabolism; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - deficiency; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factors
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.175.4.2340

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 (T(FH)) 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+ T(FH) 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+ T(FH) cells was enhanced by interaction with B cells, which was abrogated by anti-B7RP-1 mAb treatment. The development of CXCR5+ T(FH) 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+ T(FH) cells in vivo.