Abstract
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.
MeSH terms
-
Abatacept
-
Adjuvants, Immunologic / administration & dosage*
-
Administration, Cutaneous
-
Animals
-
Antigens, CD / administration & dosage
-
Antigens, Differentiation / administration & dosage
-
Asthma / immunology
-
B-Lymphocytes / immunology*
-
B7-1 Antigen / administration & dosage
-
B7-1 Antigen / immunology*
-
B7-2 Antigen
-
Bronchoalveolar Lavage Fluid / cytology
-
Bronchoalveolar Lavage Fluid / immunology
-
CTLA-4 Antigen
-
Dermatitis, Contact / immunology
-
Dermatitis, Contact / pathology
-
Drug Administration Schedule
-
Drug Combinations
-
Female
-
Hemocyanins / administration & dosage
-
Hemocyanins / immunology
-
Humans
-
Immunoconjugates*
-
Immunoglobulin Fc Fragments / administration & dosage
-
Immunoglobulin G / biosynthesis*
-
Inducible T-Cell Co-Stimulator Ligand
-
Injections, Intraperitoneal
-
Lymph Nodes / immunology
-
Lymph Nodes / pathology
-
Lymphocyte Count
-
Membrane Glycoproteins / administration & dosage
-
Mice
-
Mice, Inbred BALB C
-
Oxazolone / administration & dosage
-
Oxazolone / immunology
-
Recombinant Fusion Proteins / administration & dosage
-
Recombinant Fusion Proteins / immunology
-
Skin / immunology
-
Skin / pathology
-
Spleen / cytology
-
Spleen / immunology
-
T-Lymphocytes / immunology*
Substances
-
Adjuvants, Immunologic
-
Antigens, CD
-
Antigens, Differentiation
-
B7-1 Antigen
-
B7-2 Antigen
-
CD86 protein, human
-
CTLA-4 Antigen
-
CTLA4 protein, human
-
Cd86 protein, mouse
-
Ctla4 protein, mouse
-
Drug Combinations
-
Immunoconjugates
-
Immunoglobulin Fc Fragments
-
Immunoglobulin G
-
Inducible T-Cell Co-Stimulator Ligand
-
Membrane Glycoproteins
-
Recombinant Fusion Proteins
-
Oxazolone
-
Abatacept
-
Hemocyanins
-
keyhole-limpet hemocyanin