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 language | English (US) |
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Pages (from-to) | 1-12 |
Number of pages | 12 |
Journal | Cellular Immunology |
Volume | 183 |
Issue number | 1 |
DOIs | |
State | Published - Jan 10 1998 |
Externally published | Yes |
Keywords
- Apoptosis
- Autoimmunity
- Fas/APO-1
- Interleukin-2
- T-lymphocyte
ASJC Scopus subject areas
- Immunology