ICOS is critical for T helper cell-mediated lung mucosal inflammatory responses

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-immunoglobuli...

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Published inNature immunology Vol. 2; no. 7; pp. 597 - 604
Main Authors Coyle, Anthony J, Gonzalo, Jose Angel, Tian, Jane, Delaney, Tracy, Corcoran, Justin, Rottman, James B, Lora, Jose, Al-garawi, Amal, Kroczek, Richard, Gutierrez-Ramos, Jose Carlos
Format Journal Article
LanguageEnglish
Published United States Nature Publishing Group 01.07.2001
Subjects
Abatacept
Animals
Antibodies, Monoclonal - biosynthesis
Antigens, CD
Antigens, Differentiation - genetics
Antigens, Differentiation, T-Lymphocyte - genetics
Antigens, Differentiation, T-Lymphocyte - immunology
CD28 Antigens - genetics
CTLA-4 Antigen
CTLA-4 protein
Cytokines - biosynthesis
Gene Expression
ICOS protein
Immune response
Immunity, Mucosal - immunology
Immunoconjugates
Immunoglobulin E - biosynthesis
Inducible T-Cell Co-Stimulator Protein
Lung - immunology
Lymphocytes
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Neutralization Tests
Rats
Rats, Inbred WKY
Receptors, CCR3
Receptors, CCR4
Receptors, CCR8
Receptors, Chemokine - genetics
Respiratory Mucosa - immunology
Th1 Cells - immunology
Th2 Cells - immunology
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Summary: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.
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ISSN:1529-2908
1529-2916
DOI:10.1038/89739