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Endogenous CD4+BV8S2- T cells from TG BV8S2+ donors confer complete protection against spontaneous experimental encephalomyelitis (Sp-EAE) in TCR transgenic, RAG-/- mice.
J Neurosci Res 2003; 71(1):89-103JN

Abstract

To investigate regulatory mechanisms which naturally prevent autoimmune diseases, we adopted the genetically restricted immunodeficient (RAG-1(-/-)) myelin basic protein (MBP)-specific T cell receptor (TCR) double transgenic (T/R-) mouse model of spontaneous experimental autoimmune encephalomyelitis (Sp-EAE). Sp-EAE can be prevented after transfer of CD4+splenocytes from naïve immunocompetent mice. RAG-1+ double transgenic (T/R+) mice do not develop Sp-EAE due to the presence of a very small population (about 2%) of non-Tg TCR specificities. In this study, CD4+BV8S2+ T cells that predominate in T/R+ mice, and three additional populations, CD4+BV8S2-, CD4-CD8-BV8S2+, and CD4-CD8+BV8S2+ T cells that expanded in T/R+ mice after immunization with MBP-Ac1-11 peptide, were studied for their ability to prevent Sp-EAE in T/R- mice. Only the CD4+BV8S2- T cell population conferred complete protection against Sp-EAE, similar to unfractionated splenocytes from non-Tg donors, whereas CD4-CD8-BV8S2+ and CD4+BV8S2+ T cells conferred partial protection. In contrast, CD4-CD8+BV8S2+ T cells had no significant protective effects. The highly protective CD4+BV8S2- subpopulation was CD25+, contained non-clonotypic T cells, and uniquely expressed the CCR4 chemokine receptor. Protected recipient T/R- mice had marked increases in CD4+CD25+ Treg-like cells, retention of the pathogenic T cell phenotype in the spleen, and markedly reduced inflammation in CNS tissue. Partially protective CD4+BV8S2+ and CD4- CD8-BV8S2+ subpopulations appeared to be mainly clonotypic T cells with altered functional properties. These three Sp-EAE protective T cell subpopulations possessed distinctive properties and induced a variety of effects in T/R- recipients, thus implicating differing mechanisms of protection.

Authors+Show Affiliations

Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12478617

Citation

Matejuk, Agata, et al. "Endogenous CD4+BV8S2- T Cells From TG BV8S2+ Donors Confer Complete Protection Against Spontaneous Experimental Encephalomyelitis (Sp-EAE) in TCR Transgenic, RAG-/- Mice." Journal of Neuroscience Research, vol. 71, no. 1, 2003, pp. 89-103.
Matejuk A, Buenafe AC, Dwyer J, et al. Endogenous CD4+BV8S2- T cells from TG BV8S2+ donors confer complete protection against spontaneous experimental encephalomyelitis (Sp-EAE) in TCR transgenic, RAG-/- mice. J Neurosci Res. 2003;71(1):89-103.
Matejuk, A., Buenafe, A. C., Dwyer, J., Ito, A., Silverman, M., Zamora, A., ... Offner, H. (2003). Endogenous CD4+BV8S2- T cells from TG BV8S2+ donors confer complete protection against spontaneous experimental encephalomyelitis (Sp-EAE) in TCR transgenic, RAG-/- mice. Journal of Neuroscience Research, 71(1), pp. 89-103.
Matejuk A, et al. Endogenous CD4+BV8S2- T Cells From TG BV8S2+ Donors Confer Complete Protection Against Spontaneous Experimental Encephalomyelitis (Sp-EAE) in TCR Transgenic, RAG-/- Mice. J Neurosci Res. 2003 Jan 1;71(1):89-103. PubMed PMID: 12478617.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous CD4+BV8S2- T cells from TG BV8S2+ donors confer complete protection against spontaneous experimental encephalomyelitis (Sp-EAE) in TCR transgenic, RAG-/- mice. AU - Matejuk,Agata, AU - Buenafe,Abigail C, AU - Dwyer,Jami, AU - Ito,Atsushi, AU - Silverman,Marc, AU - Zamora,Alex, AU - Subramanian,Sandhya, AU - Vandenbark,Arthur A, AU - Offner,Halina, PY - 2002/12/13/pubmed PY - 2003/3/13/medline PY - 2002/12/13/entrez SP - 89 EP - 103 JF - Journal of neuroscience research JO - J. Neurosci. Res. VL - 71 IS - 1 N2 - To investigate regulatory mechanisms which naturally prevent autoimmune diseases, we adopted the genetically restricted immunodeficient (RAG-1(-/-)) myelin basic protein (MBP)-specific T cell receptor (TCR) double transgenic (T/R-) mouse model of spontaneous experimental autoimmune encephalomyelitis (Sp-EAE). Sp-EAE can be prevented after transfer of CD4+splenocytes from naïve immunocompetent mice. RAG-1+ double transgenic (T/R+) mice do not develop Sp-EAE due to the presence of a very small population (about 2%) of non-Tg TCR specificities. In this study, CD4+BV8S2+ T cells that predominate in T/R+ mice, and three additional populations, CD4+BV8S2-, CD4-CD8-BV8S2+, and CD4-CD8+BV8S2+ T cells that expanded in T/R+ mice after immunization with MBP-Ac1-11 peptide, were studied for their ability to prevent Sp-EAE in T/R- mice. Only the CD4+BV8S2- T cell population conferred complete protection against Sp-EAE, similar to unfractionated splenocytes from non-Tg donors, whereas CD4-CD8-BV8S2+ and CD4+BV8S2+ T cells conferred partial protection. In contrast, CD4-CD8+BV8S2+ T cells had no significant protective effects. The highly protective CD4+BV8S2- subpopulation was CD25+, contained non-clonotypic T cells, and uniquely expressed the CCR4 chemokine receptor. Protected recipient T/R- mice had marked increases in CD4+CD25+ Treg-like cells, retention of the pathogenic T cell phenotype in the spleen, and markedly reduced inflammation in CNS tissue. Partially protective CD4+BV8S2+ and CD4- CD8-BV8S2+ subpopulations appeared to be mainly clonotypic T cells with altered functional properties. These three Sp-EAE protective T cell subpopulations possessed distinctive properties and induced a variety of effects in T/R- recipients, thus implicating differing mechanisms of protection. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/12478617/Endogenous_CD4+BV8S2__T_cells_from_TG_BV8S2+_donors_confer_complete_protection_against_spontaneous_experimental_encephalomyelitis__Sp_EAE__in_TCR_transgenic_RAG_/__mice_ L2 - https://doi.org/10.1002/jnr.10450 DB - PRIME DP - Unbound Medicine ER -