Tags

Type your tag names separated by a space and hit enter

Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE).
J Exp Med. 1996 Nov 01; 184(5):1609-17.JE

Abstract

T cell receptor (TCR)-recognizing regulatory cells, induced after vaccination with self-reactive T cells or TCR peptides, have been shown to prevent autoimmunity. We have asked whether this regulation is involved in the maintenance of peripheral tolerance to myelin basic protein (MBP) in an autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). Antigen-induced EAE in (SJL x B10.PL)F1 mice is transient in that most animals recover permanently from the disease. Most of the initial encephalitogenic T cells recognize MBP Ac1-9 and predominantly use the TCR V beta 8.2 gene segment. In mice recovering from MBP-induced EAE, regulatory CD4+ T cells (Treg) specific for a single immunodominant TCR peptide B5 (76-101) from framework region 3 of the V beta 8.2 chain, become primed. We have earlier shown that cloned B5-reactive Treg can specifically downregulate responses to Ac1-9 and also protect mice from EAE. These CD4 Treg clones predominantly use the TCR V beta 14 or V beta 3 gene segments. Here we have directly tested whether deletion/blocking of the Treg from the peripheral repertoire affects the spontaneous recovery from EAE. Treatment of F1 mice with appropriate V beta-specific monoclonal antibodies resulted in an increase in the severity and duration of the disease; even relapses were seen in one-third to one-half of the Treg-deleted mice. Interestingly, chronic disease in treated mice appears to be due to the presence of Ac1-9-specific T cells. Thus, once self-tolerance to MBP is broken by immunization with the antigen in strong adjuvant, TCR peptide-specific CD4 Treg cells participate in reestablishing peripheral tolerance. Thus, a failure to generate Treg may be implicated in chronic autoimmune conditions.

Authors+Show Affiliations

Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095-1489.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8920851

Citation

Kumar, V, et al. "Inactivation of T Cell Receptor Peptide-specific CD4 Regulatory T Cells Induces Chronic Experimental Autoimmune Encephalomyelitis (EAE)." The Journal of Experimental Medicine, vol. 184, no. 5, 1996, pp. 1609-17.
Kumar V, Stellrecht K, Sercarz E. Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE). J Exp Med. 1996;184(5):1609-17.
Kumar, V., Stellrecht, K., & Sercarz, E. (1996). Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE). The Journal of Experimental Medicine, 184(5), 1609-17.
Kumar V, Stellrecht K, Sercarz E. Inactivation of T Cell Receptor Peptide-specific CD4 Regulatory T Cells Induces Chronic Experimental Autoimmune Encephalomyelitis (EAE). J Exp Med. 1996 Nov 1;184(5):1609-17. PubMed PMID: 8920851.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inactivation of T cell receptor peptide-specific CD4 regulatory T cells induces chronic experimental autoimmune encephalomyelitis (EAE). AU - Kumar,V, AU - Stellrecht,K, AU - Sercarz,E, PY - 1996/11/1/pubmed PY - 1996/11/1/medline PY - 1996/11/1/entrez SP - 1609 EP - 17 JF - The Journal of experimental medicine JO - J. Exp. Med. VL - 184 IS - 5 N2 - T cell receptor (TCR)-recognizing regulatory cells, induced after vaccination with self-reactive T cells or TCR peptides, have been shown to prevent autoimmunity. We have asked whether this regulation is involved in the maintenance of peripheral tolerance to myelin basic protein (MBP) in an autoimmune disease model, experimental autoimmune encephalomyelitis (EAE). Antigen-induced EAE in (SJL x B10.PL)F1 mice is transient in that most animals recover permanently from the disease. Most of the initial encephalitogenic T cells recognize MBP Ac1-9 and predominantly use the TCR V beta 8.2 gene segment. In mice recovering from MBP-induced EAE, regulatory CD4+ T cells (Treg) specific for a single immunodominant TCR peptide B5 (76-101) from framework region 3 of the V beta 8.2 chain, become primed. We have earlier shown that cloned B5-reactive Treg can specifically downregulate responses to Ac1-9 and also protect mice from EAE. These CD4 Treg clones predominantly use the TCR V beta 14 or V beta 3 gene segments. Here we have directly tested whether deletion/blocking of the Treg from the peripheral repertoire affects the spontaneous recovery from EAE. Treatment of F1 mice with appropriate V beta-specific monoclonal antibodies resulted in an increase in the severity and duration of the disease; even relapses were seen in one-third to one-half of the Treg-deleted mice. Interestingly, chronic disease in treated mice appears to be due to the presence of Ac1-9-specific T cells. Thus, once self-tolerance to MBP is broken by immunization with the antigen in strong adjuvant, TCR peptide-specific CD4 Treg cells participate in reestablishing peripheral tolerance. Thus, a failure to generate Treg may be implicated in chronic autoimmune conditions. SN - 0022-1007 UR - https://www.unboundmedicine.com/medline/citation/8920851/Inactivation_of_T_cell_receptor_peptide_specific_CD4_regulatory_T_cells_induces_chronic_experimental_autoimmune_encephalomyelitis__EAE__ L2 - https://rupress.org/jem/article-lookup/doi/10.1084/jem.184.5.1609 DB - PRIME DP - Unbound Medicine ER -