CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance

Todd N Eagar; Danielle M Turley; Josette Padilla; Nitin J Karandikar; Litjen Tan; Jeffrey A Bluestone; Stephen D Miller

doi:10.4049/jimmunol.172.12.7442

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CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance

Journal article

Peer reviewed

CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance

Todd N Eagar, Danielle M Turley, Josette Padilla, Nitin J Karandikar, Litjen Tan, Jeffrey A Bluestone and Stephen D Miller

The Journal of immunology (1950), Vol.172(12), pp.7442-7450

06/15/2004

DOI: 10.4049/jimmunol.172.12.7442

PMID: 15187122

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Abstract

Intravenous treatment with Ag (peptide)-coupled, ethylene carbodiimide-fixed syngeneic splenocytes (Ag-SP) is a powerful method to induce anergy in vitro and peripheral T cell tolerance in vivo. In this study, we examined the effects of Ag-SP administration on T cell activity ex vivo and in vivo using OVA-specific DO11.10 TCR transgenic T cells. Although treatment with OVA323-339-SP resulted in a strong inhibition of peptide-specific T cell recall responses in vitro, examination of the immediate effects of Ag-SP treatment on T cells in vivo demonstrated that tolerogen injection resulted in rapid T cell activation and proliferation. Although there was an increase in the number of OVA-specific DO11.10 T cells detected in the lymphoid organs, these previously tolerized T cells were strongly inhibited in mounting proliferative or inflammatory responses upon rechallenge in vivo with peptide in CFA. This unresponsiveness was reversible by treatment with anti-CTLA-4 mAb. These results are consistent with the hypothesis that Ag-SP injection induces a state of T cell anergy that is maintained by CTLA-4 engagement.

Ovalbumin - immunology

Lymphocyte Activation

Blood - immunology

Immune Tolerance

Mice, Transgenic

Adoptive Transfer

Th1 Cells - immunology

Antigens, Differentiation - physiology

CTLA-4 Antigen

Animals

T-Lymphocytes - cytology

Cell Division

Chickens

Peptide Fragments - immunology

T-Lymphocytes - immunology

Cell Differentiation

Mice

Mice, Inbred BALB C

Th1 Cells - cytology

Antigens, CD

Antigens, Differentiation - immunology

Details

Title: Subtitle: CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance
Creators: Todd N Eagar - Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA
Danielle M Turley
Josette Padilla
Nitin J Karandikar
Litjen Tan
Jeffrey A Bluestone
Stephen D Miller
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.172(12), pp.7442-7450
DOI: 10.4049/jimmunol.172.12.7442
PMID: 15187122
NLM abbreviation: J Immunol
ISSN: 0022-1767
eISSN: 1550-6606
Publisher: United States
Grant note: AI 35225 / NIAID NIH HHS AI 35294 / NIAID NIH HHS NS 34819 / NINDS NIH HHS NS 30871 / NINDS NIH HHS CA 40216 / NCI NIH HHS NS 26543 / NINDS NIH HHS
Language: English
Date published: 06/15/2004
Academic Unit: Pathology
Record Identifier: 9984047747302771

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