Interleukin-2 reverses the defect in activation-induced apoptosis in T cells from autoimmune lpr mice

Cell Immunol. 1998 Jan 10;183(1):1-12. doi: 10.1006/cimm.1997.1233.


Activated T cells from MRLlpr/lpr (lpr) mice have been shown to be resistant to TCR-induced apoptosis (activation-induced cell death) in vitro. We have found that this resistance is related to a defect in IL-2R alpha (CD25) expression and IL-2 signaling. Following primary activation, splenic T cells from 8-week old lpr mice failed to undergo apoptosis after the TCR was religated upon reculture with plate-bound anti-CD3 mAb. These cells had markedly reduced levels of IL-2 secretion and CD25 expression during primary activation in vitro; however, the cells still progressed through the cell cycle and were capable of cell division following TCR religation. Addition of exogenous IL-2 during the primary activation of 8-week-old lpr T cells overcame the defect in CD25 expression. Strikingly, these cells also became sensitive to apoptosis induction and died when the TCR was religated with anti-CD3 mAb. Viable cell recovery of both the lpr CD4+ and CD8+ subsets, as well as the CD4-CD8- subsets, was dramatically reduced under these conditions. Further investigation also revealed that the defect in activation-induced apoptosis in T cells from lpr mice was age-related. Activated T cells from young lpr mice (5 weeks old) underwent apoptosis in response to TCR ligation; these cells also expressed normal levels of CD25 following primary activation. However, as the mice aged from 5 to 8 weeks, susceptibility to TCR-mediated apoptosis in vitro was progressively lost together with the ability to express CD25. Our results suggest that before the onset of severe lymphoaccumulation, activated T cells from young lpr mice possess the capability to undergo TCR-induced apoptosis despite defective fas expression; IL-2 participates in sensitizing the cells to this death pathway. In older mice, this pathway breaks down and, together with the lack of fas-induced apoptosis, may account for the onset of severe lymphoaccumulation and autoimmunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / immunology
  • Animals
  • Apoptosis*
  • Autoimmunity / immunology
  • Cells, Cultured
  • Female
  • Interleukin-2 / immunology*
  • Interleukin-2 / pharmacology
  • Lymphocyte Activation / immunology*
  • Male
  • Mice
  • Mice, Inbred MRL lpr
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • Receptors, Interleukin-2 / biosynthesis
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*


  • Interleukin-2
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Interleukin-2