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Induction or protection from experimental autoimmune encephalomyelitis depends on the cytokine secretion profile of TCR peptide-specific regulatory CD4 T cells.
J Immunol 1998; 161(12):6585-91JI

Abstract

Autoimmune diseases can result from the breakdown of regulation and subsequent activation of self-antigenic determinant-reactive T cells. During the evolution of the autoimmune response to myelin basic protein (MBP) in B10.PL mice, several distinct T cell populations expand: the effectors mediating experimental autoimmune encephalomyelitis (EAE) are MBP-reactive, CD4+, and predominantly TCR Vbeta8.2+; in addition, at least two regulatory populations can be detected--one comprised of Vbeta14+ CD4 T cells, reactive to a framework region 3 determinant on the Vbeta8.2 chain, and a second that is CD8+ and reactive to another Vbeta8.2 determinant. The combined action of these two regulatory cell types controls disease-causing effectors, resulting in spontaneous recovery from disease. In this report, we reveal that the cytokine secretion pattern of TCR peptide-specific regulatory CD4 T cells can profoundly influence whether a type 1 or type 2 population predominates among MBP-specific CD4 effectors. The priming of type 1 regulatory T cells results in deviation of the Ag-specific effector T cell population in a type 2 direction and protection from disease. In contrast, induction of type 2 regulatory T cells results in exacerbation of EAE, poor recovery, and an increased frequency of type 1 effectors. Thus, the encephalitogenic potential of the MBP-reactive effector population is crucially and dominantly influenced by the cytokine secretion phenotype of regulatory CD4 T cells. These findings have important implications in understanding peripheral tolerance to self-Ags as well as in the design of TCR-based therapeutic approaches.

Authors+Show Affiliations

Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095, USA. Vipink@liai.orgNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9862685

Citation

Kumar, V, and E Sercarz. "Induction or Protection From Experimental Autoimmune Encephalomyelitis Depends On the Cytokine Secretion Profile of TCR Peptide-specific Regulatory CD4 T Cells." Journal of Immunology (Baltimore, Md. : 1950), vol. 161, no. 12, 1998, pp. 6585-91.
Kumar V, Sercarz E. Induction or protection from experimental autoimmune encephalomyelitis depends on the cytokine secretion profile of TCR peptide-specific regulatory CD4 T cells. J Immunol. 1998;161(12):6585-91.
Kumar, V., & Sercarz, E. (1998). Induction or protection from experimental autoimmune encephalomyelitis depends on the cytokine secretion profile of TCR peptide-specific regulatory CD4 T cells. Journal of Immunology (Baltimore, Md. : 1950), 161(12), pp. 6585-91.
Kumar V, Sercarz E. Induction or Protection From Experimental Autoimmune Encephalomyelitis Depends On the Cytokine Secretion Profile of TCR Peptide-specific Regulatory CD4 T Cells. J Immunol. 1998 Dec 15;161(12):6585-91. PubMed PMID: 9862685.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction or protection from experimental autoimmune encephalomyelitis depends on the cytokine secretion profile of TCR peptide-specific regulatory CD4 T cells. AU - Kumar,V, AU - Sercarz,E, PY - 1998/12/23/pubmed PY - 1998/12/23/medline PY - 1998/12/23/entrez SP - 6585 EP - 91 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 161 IS - 12 N2 - Autoimmune diseases can result from the breakdown of regulation and subsequent activation of self-antigenic determinant-reactive T cells. During the evolution of the autoimmune response to myelin basic protein (MBP) in B10.PL mice, several distinct T cell populations expand: the effectors mediating experimental autoimmune encephalomyelitis (EAE) are MBP-reactive, CD4+, and predominantly TCR Vbeta8.2+; in addition, at least two regulatory populations can be detected--one comprised of Vbeta14+ CD4 T cells, reactive to a framework region 3 determinant on the Vbeta8.2 chain, and a second that is CD8+ and reactive to another Vbeta8.2 determinant. The combined action of these two regulatory cell types controls disease-causing effectors, resulting in spontaneous recovery from disease. In this report, we reveal that the cytokine secretion pattern of TCR peptide-specific regulatory CD4 T cells can profoundly influence whether a type 1 or type 2 population predominates among MBP-specific CD4 effectors. The priming of type 1 regulatory T cells results in deviation of the Ag-specific effector T cell population in a type 2 direction and protection from disease. In contrast, induction of type 2 regulatory T cells results in exacerbation of EAE, poor recovery, and an increased frequency of type 1 effectors. Thus, the encephalitogenic potential of the MBP-reactive effector population is crucially and dominantly influenced by the cytokine secretion phenotype of regulatory CD4 T cells. These findings have important implications in understanding peripheral tolerance to self-Ags as well as in the design of TCR-based therapeutic approaches. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9862685/Induction_or_protection_from_experimental_autoimmune_encephalomyelitis_depends_on_the_cytokine_secretion_profile_of_TCR_peptide_specific_regulatory_CD4_T_cells_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9862685 DB - PRIME DP - Unbound Medicine ER -