9-cis-retinoic acid inhibits activation-driven T-cell apoptosis: implications for retinoid X receptor involvement in thymocyte development. |
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| Authors: | Y Yang M S Vacchio J D Ashwell |
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| Affiliation: | Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892. |
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| Abstract: | Retinoic acid is a morphogenetic signaling molecule derived from vitamin A and involved in vertebrate development. Two groups of receptors, retinoic acid receptors and retinoid X receptors (RXRs), have been identified. All-trans-retinoic acid is the high-affinity ligand for retinoic acid receptors, and 9-cis-retinoic acid additionally binds RXRs with high affinity. Here we report that although retinoic acid has little inhibitory effect on activation-induced T-cell proliferation, it specifically prevents activation-induced apoptosis of T-cell hybridomas and antigen-specific deletion of immature CD4+CD8+ thymocytes from alpha beta T-cell receptor transgenic mice. 9-cis-Retinoic acid was approximately 10-fold more potent than all-trans-retinoic acid, suggesting that RXRs participate in this process. Thus, although 9-cis-retinoic acid has little immuno-suppressive activity, it is a potent negative regulator of activation-induced T-cell apoptosis, raising the possibility that RXRs may take part in regulating T-cell development. |
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