Inducible costimulatory molecule-B7-related protein 1 interactions are important for the clonal expansion and B cell helper functions of naive, Th1, and Th2 T cells.
Inducing T cell responses requires at least two distinct signals: 1) TCR engagement of MHC-peptide and 2) binding of CD28 to B7.1/2. However, the recent avalanche of newly described costimulatory molecules may represent additional signals which can modify events after the initial two-signal activation. Inducible costimulatory molecule (ICOS) is a CD28 family member expressed on T cells rapidly following activation that augments both Th1 and Th2 T cell responses and has been implicated in sustaining rather than initiating T cell responses. Although it is known that blockade of ICOS-B7-related protein 1 (B7RP-1) in vivo dramatically reduces germinal center formation and Ab production, the mechanism(s) remains unclear. An optimal T cell-dependent Ab response requires T and B cell activation, expansion, differentiation, survival, and migration, and the ICOS-B7RP-1 interaction could be involved in any or all of these processes. Understanding this will have important implications for targeting ICOS-B7RP-1 therapeutically. We have therefore used a double-adoptive transfer system, in which all of the above events can be analyzed, to assess the role of ICOS-B7RP-1 in T cell help for B cell responses. We have shown that ICOS signaling is involved in the initial clonal expansion of primary and primed Th1 and Th2 cells in response to immunization. Furthermore, while ICOS-B7RP-1 interactions have no effect on the migration of T cells into B cell follicles, it is essential for their ability to support B cell responses.
Smith
Karen M
KM
Department of Immunology and Bacteriology, University of Glasgow, Glasgow, UK.
Brewer
James M
JM
Webb
Phillip
P
Coyle
Anthony J
AJ
Gutierrez-Ramos
Carlos
C
Garside
Paul
P
D019264:Adoptive Transfer; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018122:B7-1 Antigen / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002999:Clone Cells; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006131:Growth Inhibitors / Q000008:administration & dosage; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007274:Injections, Intraperitoneal; D007399:Interphase / Q000276:immunology; D008211:Lymphocyte Cooperation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D015398:Signal Transduction / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D006131:Growth Inhibitors; C556694:Icos protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein