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

Laszlo G. Radvanyi, Kaliannan Raju, David Spaner, Gordon Mills, Richard G. Miller

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Activated T cells from MRL(lpr/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-2Rα (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.

Original languageEnglish (US)
Pages (from-to)1-12
Number of pages12
JournalCellular Immunology
Volume183
Issue number1
DOIs
StatePublished - Jan 10 1998
Externally publishedYes

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Interleukin-2
Apoptosis
T-Lymphocytes
Cell Death
Autoimmunity
Cell Division
Ligation
Cell Cycle
In Vitro Techniques

Keywords

  • Apoptosis
  • Autoimmunity
  • Fas/APO-1
  • Interleukin-2
  • T-lymphocyte

ASJC Scopus subject areas

  • Immunology

Cite this

Interleukin-2 reverses the defect in activation-induced apoptosis in T cells from autoimmune Ipr mice. / Radvanyi, Laszlo G.; Raju, Kaliannan; Spaner, David; Mills, Gordon; Miller, Richard G.

In: Cellular Immunology, Vol. 183, No. 1, 10.01.1998, p. 1-12.

Research output: Contribution to journalArticle

Radvanyi, Laszlo G. ; Raju, Kaliannan ; Spaner, David ; Mills, Gordon ; Miller, Richard G. / Interleukin-2 reverses the defect in activation-induced apoptosis in T cells from autoimmune Ipr mice. In: Cellular Immunology. 1998 ; Vol. 183, No. 1. pp. 1-12.
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