title: Functional hierarchy and relative contribution of the CD28/B7 and ICOS/B7-H2 costimulatory pathways to T cell-mediated delayed-type hypersensitivity.
abstract: The CD28/B7 and ICOS/B7-H2 pathways are both critical for costimulating T cell immune responses. Deficiency in either pathway results in defective T cell activation, cytokine production and germinal center formation. However, the relative importance and contribution of each pathway towards T cell-mediated immunity is still not clear. To address this issue, we compared T cell responses of WT, CD28 knockout (KO), B7-H2 KO, and CD28-B7-H2 double KO (DKO) mice in a model of delayed-type hypersensitivity (DTH). While CD28 KO mice have partially compromised DTH response, DKO mice exhibited greatly diminished response, suggesting that the ICOS/B7-H2 pathway could partially compensate for the costimulation of DTH. Surprisingly, B7-H2 KO mice had comparable DTH response as WT mice, indicating that the ICOS/B7-H2 pathway is secondary to the CD28/B7 pathway in costimulating DTH. Interestingly, prolonging the period of sensitization could overcome the compromised DTH response in CD28 KO but not DKO mice, revealing a novel form of functional redundancy of ICOS/B7-H2 costimulation that is dependent on time to take effect. Taken together, our data reveal a functional hierarchy of the CD28/B7 and ICOS/B7-H2 pathways and delineated their relative contributions to the elicitation of a DTH response.
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research, Singapore, Singapore.
authors.forename: Siew-Cheng
authors.initials: SC
authors.lastname: Wong
authors.forename: Andy Hee-Meng
authors.initials: AH
authors.lastname: Tan
authors.forename: Kong-Peng
authors.initials: KP
authors.lastname: Lam
mesh_terms: D000818:Animals; D000941:Antigens / Q000008:administration & dosage; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D066298:In Vitro Techniques; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D000941:Antigens; D000945:Antigens, Differentiation, T-Lymphocyte; D018122:B7-1 Antigen; D018106:CD28 Antigens; C556694:Icos protein, mouse; C400230:Icosl protein, mouse; D060945:Inducible T-Cell Co-Stimulator Ligand; D060889:Inducible T-Cell Co-Stimulator Protein; D011506:Proteins; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D007371:Interferon-gamma