CD4+CD8- thymocytes that express L-selectin protect rats from diabetes upon adoptive transfer

Eur J Immunol. 1996 Nov;26(11):2702-8. doi: 10.1002/eji.1830261123.

Abstract

Previous studies have shown that insulin-dependent diabetes can be induced in normal PVG.RT1u rats by a protocol of adult thymectomy and irradiation. The injection of CD4+ T cells from non-irradiated syngeneic donors prevents the onset of disease in approximately 50% of pre-diabetic recipients but all rats are protected if a particular subset of CD4+ cells is transferred. These protective cells express TCR alpha beta and have a memory phenotype, being CD45RClow RT6+. Further studies have demonstrated that the transfer of CD4+CD8- thymocytes, like that of unfractionated CD4+ peripheral T cells, also protects approximately half of recipients from diabetes suggesting that, as with the peripheral T cells, a functional heterogeneity may exist amongst CD4+CD8- thymocytes. In this study, we show that L-selectin is expressed by 50-60% of all CD4+CD8- thymocytes from 6-week-old rats. Adoptive transfer of these populations into thymectomized and irradiated rats revealed that the protection from diabetes observed by CD4+CD8- thymocytes was mediated almost entirely by the L-selectin+ subset. Cells with this phenotype were also able to mediate both humoral and cell mediated responses, providing primed B cells with help for secondary antibody responses and mediating local graft-versus-host reactions. L-selectin- CD4+CD8- thymocytes failed to mediate these responses. These data indicate that CD4+CD8- thymocytes must mature to the stage of L-selectin expression, before they can mediate normal T cell function. The implications of these results are discussed with respect to the possible role of murine NK1.1+ thymocytes in the control of autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer*
  • Animals
  • Antibodies, Monoclonal / immunology
  • CD4 Antigens / analysis*
  • CD8 Antigens / analysis*
  • Cytokines / biosynthesis
  • Diabetes Mellitus, Type 1 / immunology*
  • Graft vs Host Reaction / immunology
  • L-Selectin / biosynthesis*
  • Rats
  • Rats, Inbred Strains
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocyte Subsets / transplantation*
  • Th1 Cells / metabolism
  • Thymus Gland / cytology*
  • Thymus Gland / immunology

Substances

  • Antibodies, Monoclonal
  • CD4 Antigens
  • CD8 Antigens
  • Cytokines
  • L-Selectin