Abstract
We examined the requirement for and cooperation between CD28 and inducible costimulator (ICOS) in effective T helper (TH) cell responses in vivo. We found that both CD28 and ICOS were critical in determining the outcome of an immune response; cytolytic T lymphocyte-associated antigen 4-immunoglobulin (CTLA-4-Ig), ICOS-Ig and/or a neutralizing ICOS monoclonal antibody attenuated T cell expansion, TH2 cytokine production and eosinophilic inflammation. CD28-dependent signaling was essential during priming, whereas ICOS-B7RP-1 regulated TH effector responses, and the up-regulation of chemokine receptors that determine T cell migration. Our data suggests a scenario whereby both molecules regulate the outcome of the immune response but play separate key roles: CD28 primes T cells and ICOS regulates effector responses.
MeSH terms
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Abatacept
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Animals
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Antibodies, Monoclonal / biosynthesis
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Antigens, CD
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Antigens, Differentiation / genetics
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology*
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CD28 Antigens / genetics
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CTLA-4 Antigen
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Cytokines / biosynthesis
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Gene Expression
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Immunity, Mucosal / immunology
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Immunoconjugates*
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Immunoglobulin E / biosynthesis
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Inducible T-Cell Co-Stimulator Protein
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Lung / immunology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Neutralization Tests
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Rats
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Rats, Inbred WKY
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Receptors, CCR3
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Receptors, CCR4
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Receptors, CCR8
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Receptors, Chemokine / genetics
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Respiratory Mucosa / immunology
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Th1 Cells / immunology*
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Th2 Cells / immunology*
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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Antigens, Differentiation, T-Lymphocyte
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CCR3 protein, human
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CCR4 protein, human
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CCR8 protein, human
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CD28 Antigens
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CTLA-4 Antigen
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CTLA4 protein, human
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Ccr3 protein, mouse
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Ccr3 protein, rat
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Ccr4 protein, mouse
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Ccr4 protein, rat
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Ctla4 protein, mouse
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Ctla4 protein, rat
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Cytokines
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ICOS protein, human
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Icos protein, mouse
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Icos protein, rat
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Immunoconjugates
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Inducible T-Cell Co-Stimulator Protein
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Receptors, CCR3
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Receptors, CCR4
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Receptors, CCR8
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Receptors, Chemokine
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Immunoglobulin E
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Abatacept