Bag-1 up-regulation in anti-CD4 mAb treated allo-activated T cells confers resistance to apoptosis
✍ Scribed by Birgit Sawitzki; Manfred Lehmann; Katrin Vogt; Kirsten Risch; Josef Brock; Jerzy W. Kupiec-Weglinski; Hans-Dieter Volk
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 161 KB
- Volume
- 32
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
The nondepleting anti-CD4 mAb RIB5/2 is a powerful inducer of tolerance to MHCincompatible renal and heart allografts in rat recipients. In vitro the mAb blocks the proliferation and cytokine production of alloreactive T cells. To learn more about the mechanism of anti-CD4-mediated suppression, we applied differential display reverse transcription-PCR to identify differences at mRNA level between T cells stimulated by alloantigen in the presence or absence of anti-CD4 mAb. A sequence alignment of a 550-bp DNA fragment appearing only in anti-CD4 mAb-treated cells resulted in at least 95% homology to a mouse cDNA encoding for the anti-apoptotic protein Bag-1. Further investigation of Bag-1 expression during mixed lymphocyte reactions revealed a three-to fourfold up-regulation of Bag-1 mRNA expression in anti-CD4 mAb-treated allogeneic cultures which was confirmed at protein level. Bag-1 up-regulation was associated with an increase resistance to apoptosis of T cells from anti-CD4 mAb-treated cultures. Application of antisense oligonucleotides specific for Bag-1 reduced Bag-1 protein expression and restored susceptibility to apoptosis. In addition, up-regulation of Bag-1 mRNA could also be detected in graft-infiltrating T cells from anti-CD4 mAb-treated rats in vivo. Thus, the expression of Bag-1 in a subset of anti-CD4 mAb-treated alloreactive T cells conferred resistance against apoptosis, potentially contributing to the long-term survival of these cells.