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Coculture of TCR peptide-specific T cells with basic protein-specific T cells inhibits proliferation, IL-3 mRNA, and transfer of experimental autoimmune encephalomyelitis.
J Immunol. 1994 Dec 01; 153(11):4988-96.JI

Abstract

TCR peptides, namely V beta 8.2-39-59 or the minimal idiotope, V beta 8-44-54, can treat experimental autoimmune encephalomyelitis (EAE) in Lewis rats, presumably by activating naturally induced TCR peptide-specific T cells that arise in response to the focused appearance of V beta 8.2+ encephalitogenic T cells. The purpose of the present study was to evaluate the mechanisms by which TCR peptides inhibit EAE. We found that treatment of EAE with the V beta 8.2-39-59 peptide did not induce any evidence of DNA fragmentation (apoptosis) in spinal cord cells isolated from clinically well rats, implicating a regulatory rather than a deletional mechanism. TCR peptide-specific T cell lines failed to inhibit EAE induced by already activated BP-specific T cells when the two T cell specificities were co-injected. However, coculturing the encephalitogenic T cells in the presence of the regulatory T cells during the activation step before transfer almost completely inhibited the induction of EAE. Inhibition could be induced by direct contact between the two cell types or by soluble factors produced in a transwell system, but was greatly enhanced when soluble V beta 8.2-39-59 peptide was used to optimally activate the regulatory T cells. The inhibition was regulatory cell dose dependent, and was reflected in vitro by reduced proliferation response and mRNA production for IL-3, and to a lesser extent, IFN-gamma and IL-2. These results indicate that regulation induced by TCR peptides involves cell-cell interactions that lead to the production and release of soluble factors that locally inhibit the activation of encephalitogenic T cells expressing MHC-bound idiotopes of the target V beta-chain, and possibly "bystander" specificities expressing different V beta-chains.

Authors+Show Affiliations

Veterans Affairs Medical Center, Portland, OR 97201.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

7525721

Citation

Offner, H, et al. "Coculture of TCR Peptide-specific T Cells With Basic Protein-specific T Cells Inhibits Proliferation, IL-3 mRNA, and Transfer of Experimental Autoimmune Encephalomyelitis." Journal of Immunology (Baltimore, Md. : 1950), vol. 153, no. 11, 1994, pp. 4988-96.
Offner H, Vainiene M, Celnik B, et al. Coculture of TCR peptide-specific T cells with basic protein-specific T cells inhibits proliferation, IL-3 mRNA, and transfer of experimental autoimmune encephalomyelitis. J Immunol. 1994;153(11):4988-96.
Offner, H., Vainiene, M., Celnik, B., Weinberg, A. D., Buenafe, A., & Vandenbark, A. A. (1994). Coculture of TCR peptide-specific T cells with basic protein-specific T cells inhibits proliferation, IL-3 mRNA, and transfer of experimental autoimmune encephalomyelitis. Journal of Immunology (Baltimore, Md. : 1950), 153(11), 4988-96.
Offner H, et al. Coculture of TCR Peptide-specific T Cells With Basic Protein-specific T Cells Inhibits Proliferation, IL-3 mRNA, and Transfer of Experimental Autoimmune Encephalomyelitis. J Immunol. 1994 Dec 1;153(11):4988-96. PubMed PMID: 7525721.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Coculture of TCR peptide-specific T cells with basic protein-specific T cells inhibits proliferation, IL-3 mRNA, and transfer of experimental autoimmune encephalomyelitis. AU - Offner,H, AU - Vainiene,M, AU - Celnik,B, AU - Weinberg,A D, AU - Buenafe,A, AU - Vandenbark,A A, PY - 1994/12/1/pubmed PY - 1994/12/1/medline PY - 1994/12/1/entrez SP - 4988 EP - 96 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 153 IS - 11 N2 - TCR peptides, namely V beta 8.2-39-59 or the minimal idiotope, V beta 8-44-54, can treat experimental autoimmune encephalomyelitis (EAE) in Lewis rats, presumably by activating naturally induced TCR peptide-specific T cells that arise in response to the focused appearance of V beta 8.2+ encephalitogenic T cells. The purpose of the present study was to evaluate the mechanisms by which TCR peptides inhibit EAE. We found that treatment of EAE with the V beta 8.2-39-59 peptide did not induce any evidence of DNA fragmentation (apoptosis) in spinal cord cells isolated from clinically well rats, implicating a regulatory rather than a deletional mechanism. TCR peptide-specific T cell lines failed to inhibit EAE induced by already activated BP-specific T cells when the two T cell specificities were co-injected. However, coculturing the encephalitogenic T cells in the presence of the regulatory T cells during the activation step before transfer almost completely inhibited the induction of EAE. Inhibition could be induced by direct contact between the two cell types or by soluble factors produced in a transwell system, but was greatly enhanced when soluble V beta 8.2-39-59 peptide was used to optimally activate the regulatory T cells. The inhibition was regulatory cell dose dependent, and was reflected in vitro by reduced proliferation response and mRNA production for IL-3, and to a lesser extent, IFN-gamma and IL-2. These results indicate that regulation induced by TCR peptides involves cell-cell interactions that lead to the production and release of soluble factors that locally inhibit the activation of encephalitogenic T cells expressing MHC-bound idiotopes of the target V beta-chain, and possibly "bystander" specificities expressing different V beta-chains. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/7525721/Coculture_of_TCR_peptide_specific_T_cells_with_basic_protein_specific_T_cells_inhibits_proliferation_IL_3_mRNA_and_transfer_of_experimental_autoimmune_encephalomyelitis_ L2 - https://www.jimmunol.org/lookup/pmidlookup?view=long&pmid=7525721 DB - PRIME DP - Unbound Medicine ER -