Autoreactive and immunoregulatory T-cell subsets in insulin-dependent diabetes mellitus

Diabetologia. 1999 Apr;42(4):443-9. doi: 10.1007/s001250051177.


Aims/hypothesis: Type I (insulin-dependent) diabetes mellitus is a T-cell mediated autoimmune disease. Several subsets of T-cells, in particular CD4+ and in vivo activate CD45RA+RO+ T-cells, have been shown to be increased at disease onset. The functional implications of these relative increases in CD4 T-cells were investigated.

Methods: Subsets of T-cells were sorted on the basis of their activation status (CD45RA+ naive cells, CD45RA+RO+ recently activated cells and CD45RO+ memory cells) and stimulated with autoantigens or recall antigen in vitro.

Results: Proliferative responses to tetanus toxoid were primarily or exclusively observed in resting memory T-cells (CD45RO+). Autoimmune T-cell responses were, however, primarily measured in activated T-cells (CD45RA+RO+) in newly diagnosed Type I diabetic patients, whereas those with longer disease duration reacted to autoantigens with memory T-cells (CD45RO+) (p < 0.004). Interestingly, in non-diabetic control subjects not responding to autoantigens in the regular assay, considerable autoreactive T-cell responses were detectable after sorting in the CD45RO+ or CD45RA+RO+ lymphocyte subsets. Remixing these subsets showed that these autoimmune responses in activated cells could be down-modulated by CD45RA+ lymphocytes, whereas resting memory cells appeared unaffected by the suppressive CD45RA subset.

Conclusion/interpretation: These results show that autoimmune T-cell responses can be linked to particular subsets which differ depending on clinical status. Furthermore, the CD45RA T-cell subset harbours lymphocytes potentially capable of suppressing autoimmune T-cell responses. The changes in responsiveness to exogenous insulin may help to unravel the mechanism by which isohormonal therapy could prevent the onset of Type I diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Cell Division
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Insulin / metabolism
  • Leukocyte Common Antigens / metabolism
  • Male
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Rats
  • T-Lymphocyte Subsets / immunology*
  • Tumor Cells, Cultured


  • Insulin
  • Leukocyte Common Antigens
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1