The role of ICOS in the CXCR5+ follicular B helper T cell maintenance in vivo.
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.
Akiba
Hisaya
H
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan. hisaya@med.juntendo.ac.jp
Takeda
Kazuyoshi
K
Kojima
Yuko
Y
Usui
Yoshihiko
Y
Harada
Norihiro
N
Yamazaki
Tomohide
T
Ma
Juan
J
Tezuka
Katsunari
K
Yagita
Hideo
H
Okumura
Ko
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000954:Antigens, Surface / Q000096:biosynthesis / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology; D018106:CD28 Antigens / Q000235:genetics / Q000502:physiology; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D019743:Chemokines, CXC / Q000378:metabolism; D005260:Female; D018858:Germinal Center / Q000166:cytology / Q000276:immunology; D007117:Immunization, Secondary; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D016513:Mice, SCID; D053278:OX40 Ligand; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D018121:Receptors, Cytokine / Q000096:biosynthesis*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D048069:Tumor Necrosis Factors
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D018122:B7-1 Antigen; D018106:CD28 Antigens; D019013:CD40 Antigens; C513179:CXCR5 protein, mouse; D019743:Chemokines, CXC; C556692:ICOS protein, human; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D053278:OX40 Ligand; D054380:Receptors, CXCR5; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; C504586:Tnfsf4 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors