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

Research output: Contribution to journalArticle

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

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.

Original languageEnglish (US)
Pages (from-to)7442-7450
Number of pages9
JournalJournal of Immunology
Volume172
Issue number12
DOIs
StatePublished - Jun 15 2004

PMID: 15187122

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CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance. / Eagar, Todd N.; Turley, Danielle M.; Padilla, Josette; Karandikar, Nitin J.; Tan, Litjen; Bluestone, Jeffrey A.; Miller, Stephen D.

In: Journal of Immunology, Vol. 172, No. 12, 15.06.2004, p. 7442-7450.

Research output: Contribution to journalArticle

Harvard

Eagar, TN, Turley, DM, Padilla, J, Karandikar, NJ, Tan, L, Bluestone, JA & Miller, SD 2004, 'CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance' Journal of Immunology, vol. 172, no. 12, pp. 7442-7450. https://doi.org/10.4049/jimmunol.172.12.7442

APA

Eagar, T. N., Turley, D. M., Padilla, J., Karandikar, N. J., Tan, L., Bluestone, J. A., & Miller, S. D. (2004). CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance. Journal of Immunology, 172(12), 7442-7450. https://doi.org/10.4049/jimmunol.172.12.7442

Vancouver

Eagar TN, Turley DM, Padilla J, Karandikar NJ, Tan L, Bluestone JA et al. CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance. Journal of Immunology. 2004 Jun 15;172(12):7442-7450. https://doi.org/10.4049/jimmunol.172.12.7442

Author

Eagar, Todd N. ; Turley, Danielle M. ; Padilla, Josette ; Karandikar, Nitin J. ; Tan, Litjen ; Bluestone, Jeffrey A. ; Miller, Stephen D. / CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance. In: Journal of Immunology. 2004 ; Vol. 172, No. 12. pp. 7442-7450.

BibTeX

@article{66661315066b41abbdc68d1de2540fb4,
title = "CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance",
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.",
author = "Eagar, {Todd N.} and Turley, {Danielle M.} and Josette Padilla and Karandikar, {Nitin J.} and Litjen Tan and Bluestone, {Jeffrey A.} and Miller, {Stephen D.}",
year = "2004",
month = "6",
day = "15",
doi = "10.4049/jimmunol.172.12.7442",
language = "English (US)",
volume = "172",
pages = "7442--7450",
journal = "Journal of Immunology",
issn = "0022-1767",
number = "12",

}

RIS

TY - JOUR

T1 - CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance

AU - Eagar, Todd N.

AU - Turley, Danielle M.

AU - Padilla, Josette

AU - Karandikar, Nitin J.

AU - Tan, Litjen

AU - Bluestone, Jeffrey A.

AU - Miller, Stephen D.

PY - 2004/6/15

Y1 - 2004/6/15

N2 - 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.

AB - 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.

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UR - http://www.scopus.com/inward/citedby.url?scp=2942586924&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.172.12.7442

DO - 10.4049/jimmunol.172.12.7442

M3 - Article

VL - 172

SP - 7442

EP - 7450

JO - Journal of Immunology

T2 - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -

ID: 16807825