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Mature mainstream TCR alpha beta+CD4+ thymocytes expressing L-selectin mediate "active tolerance" in the nonobese diabetic mouse.
J Immunol. 1998 Sep 01; 161(5):2620-8.JI

Abstract

Pathogenic autoreactive T lymphocytes are mediators of spontaneous insulin-dependent diabetes in nonobese diabetic (NOD) mice. This is demonstrated by their capacity to transfer diabetes into syngeneic immunoincompetent recipients. In addition, especially in prediabetic NOD mice, peripheral CD4+ T lymphocytes were identified that are highly effective, in conventional mixing cotransfer experiments, at preventing disease transfer. The present data demonstrate that mature heat-stable Ag-TCR alpha beta+CD8-thymocytes from prediabetic NOD mice also express this inhibitory capacity. Selection using an L-selectin (CD62L)-specific Ab showed that TCR alpha/beta+CD4+CD62L+ thymocytes, emerging from the mainstream differentiation pathway, concentrate this ability to regulate autoreactive effectors. Compared with mature TCR alpha beta+CD8- thymocytes, significantly lower numbers of TCR alpha beta+CD4+CD62L+ were sufficient to achieve an efficient inhibition of disease transfer into NOD-scid recipients. This protective ability was potentiated following in vitro culture in the presence of IL-7. In contrast, TCR alpha beta+CD62L- thymocytes, highly enriched in class I-restricted NK T cells, were unable to influence diabetes transfer. Identical results were obtained using thymocytes that have been cultured in vitro for 4 days in the presence of IL-7. These results support the active role in NOD mice of a thymus-derived CD4+ subset that controls peripheral pathogenic autoimmune effectors.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale, Unité 25, Hôpital Necker, Paris, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

9725264

Citation

Herbelin, A, et al. "Mature Mainstream TCR Alpha beta+CD4+ Thymocytes Expressing L-selectin Mediate "active Tolerance" in the Nonobese Diabetic Mouse." Journal of Immunology (Baltimore, Md. : 1950), vol. 161, no. 5, 1998, pp. 2620-8.
Herbelin A, Gombert JM, Lepault F, et al. Mature mainstream TCR alpha beta+CD4+ thymocytes expressing L-selectin mediate "active tolerance" in the nonobese diabetic mouse. J Immunol. 1998;161(5):2620-8.
Herbelin, A., Gombert, J. M., Lepault, F., Bach, J. F., & Chatenoud, L. (1998). Mature mainstream TCR alpha beta+CD4+ thymocytes expressing L-selectin mediate "active tolerance" in the nonobese diabetic mouse. Journal of Immunology (Baltimore, Md. : 1950), 161(5), 2620-8.
Herbelin A, et al. Mature Mainstream TCR Alpha beta+CD4+ Thymocytes Expressing L-selectin Mediate "active Tolerance" in the Nonobese Diabetic Mouse. J Immunol. 1998 Sep 1;161(5):2620-8. PubMed PMID: 9725264.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mature mainstream TCR alpha beta+CD4+ thymocytes expressing L-selectin mediate "active tolerance" in the nonobese diabetic mouse. AU - Herbelin,A, AU - Gombert,J M, AU - Lepault,F, AU - Bach,J F, AU - Chatenoud,L, PY - 1998/9/2/pubmed PY - 1998/9/2/medline PY - 1998/9/2/entrez SP - 2620 EP - 8 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 161 IS - 5 N2 - Pathogenic autoreactive T lymphocytes are mediators of spontaneous insulin-dependent diabetes in nonobese diabetic (NOD) mice. This is demonstrated by their capacity to transfer diabetes into syngeneic immunoincompetent recipients. In addition, especially in prediabetic NOD mice, peripheral CD4+ T lymphocytes were identified that are highly effective, in conventional mixing cotransfer experiments, at preventing disease transfer. The present data demonstrate that mature heat-stable Ag-TCR alpha beta+CD8-thymocytes from prediabetic NOD mice also express this inhibitory capacity. Selection using an L-selectin (CD62L)-specific Ab showed that TCR alpha/beta+CD4+CD62L+ thymocytes, emerging from the mainstream differentiation pathway, concentrate this ability to regulate autoreactive effectors. Compared with mature TCR alpha beta+CD8- thymocytes, significantly lower numbers of TCR alpha beta+CD4+CD62L+ were sufficient to achieve an efficient inhibition of disease transfer into NOD-scid recipients. This protective ability was potentiated following in vitro culture in the presence of IL-7. In contrast, TCR alpha beta+CD62L- thymocytes, highly enriched in class I-restricted NK T cells, were unable to influence diabetes transfer. Identical results were obtained using thymocytes that have been cultured in vitro for 4 days in the presence of IL-7. These results support the active role in NOD mice of a thymus-derived CD4+ subset that controls peripheral pathogenic autoimmune effectors. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/9725264/Mature_mainstream_TCR_alpha_beta+CD4+_thymocytes_expressing_L_selectin_mediate_"active_tolerance"_in_the_nonobese_diabetic_mouse_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9725264 DB - PRIME DP - Unbound Medicine ER -