Stimulatory effects of B7-related protein-1 on cellular and humoral immune responses in mice.
Inducible costimulator (ICOS) and B7-related protein-1 (B7RP-1) constitute a receptor-ligand pair involved in T cell costimulation. In this study, the stimulatory effects of B7RP-1 on cellular and humoral immune responses were investigated giving mice a construct with the extracellular domain of murine B7RP-1 fused with human IgG1 Fc (B7RP-1-Fc). B7RP-1-Fc stimulated contact hypersensitivity (CH) given near either the time of sensitization or challenge with oxazolone. When given near challenge time, B7RP-1-Fc stimulated CH more than a construct containing the extracellular domain of murine B7.2 and Fc (B7.2-Fc). B7RP-1-Fc increased the number of cells in lymph nodes draining the skin sensitized with oxazolone, especially activated T cells. B7RP-1-Fc also increased the ability of the cells in these lymph nodes to induce CH when transfused into naive mice. B7RP-1-Fc stimulated the production of anti-keyhole limpet hemocyanin (KLH) Ab, increasing anti-KLH IgG, IgG2a, and IgE, whereas B7.2-Fc did not affect this production. B7RP-1-Fc also increased the number of cells in lymph nodes draining the skin immunized with KLH and their production of IFN-gamma, IL-4, and IL-10 in response to KLH. Finally, B7RP-1-Fc increased the presence of eosinophils in the bronchoalveolar lavage and lungs of mice sensitized and challenged with OVA so to mount an asthmatic reaction. B7RP-1-Fc stimulates both cellular and humoral immune responses in vivo by increasing number and function of T and B cells reacting to Ag exposure.
Guo
J
J
Amgen Inc., Thousand Oaks, CA 91320, USA.
Stolina
M
M
Bready
J V
JV
Yin
S
S
Horan
T
T
Yoshinaga
S K
SK
Senaldi
G
G
D000069594:Abatacept; D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000279:Administration, Cutaneous; D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage; D000943:Antigens, Differentiation / Q000008:administration & dosage; D001249:Asthma / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000008:administration & dosage / Q000276:immunology*; D051940:B7-2 Antigen; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D060908:CTLA-4 Antigen; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage; D007074:Immunoglobulin G / Q000096:biosynthesis*; D060945:Inducible T-Cell Co-Stimulator Ligand; D007274:Injections, Intraperitoneal; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D010081:Oxazolone / Q000008:administration & dosage / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C497965:Cd86 protein, mouse; C556707:Ctla4 protein, mouse; D004338:Drug Combinations; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D060945:Inducible T-Cell Co-Stimulator Ligand; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D010081:Oxazolone; D000069594:Abatacept; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin