9-cis-retinoic acid inhibits activation-driven T-cell apoptosis: implications for retinoid X receptor involvement in thymocyte development.
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.
Yang
Y
Y
Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Vacchio
M S
MS
Ashwell
J D
JD
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D006825:Hybridomas; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D014157:Transcription Factors; D014212:Tretinoin / Q000494:pharmacology*
D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin