Cross-Linking the TCR Complex Induces Apoptosis in CD4 8 Thymocytes in the Presence of Cyclosporin AReportar como inadecuado

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Developmental Immunology - Volume 5 1996, Issue 1, Pages 1-15

The University of Texas, M.D. Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, Texas 78957, USA

Received 1 December 1995; Accepted 14 February 1996

Copyright © 1996 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Although it is generally agreed that TCR ligation is a minimal requirement for negativeselection in the CD


double-positive DP thymocyte subset, the costimulatory requirementsand specific signaling events necessary to induce apoptosis are not well defined. Wehave explored the consequences of cross-linking CD3-TCR complexes on thymocytes fromH-Y TCR transgenic Tg mice. In agreement with previous reports, we demonstrate thatculturing DP thymocytes with plate-bound anti-TCR antibody induces downregulation ofCD4 and CD8 and upregulation of CD69 expression. Nevertheless, the activated cells didnot undergo apoptosis, as determined by viable cell recoveries and by quantitation of DNAfragmentation using the TUNEL assay. However, specific depletion of the DP subset occurredwithin 24 hr when thymocytes were incubated in the presence of both anti-TCR andthe immunosuppressant cyclosporin A CsA. CsA also induced depletion of anti-CD3stimulated normal DP thymocytes. Using mice homozygous for the lpr or gld mutation, wealso have shown that Fas-Fas ligand interactions are not involved in the CsA-induceddeath of TCR-stimulated DP thymocytes. These data verify that TCR cross-linking aloneis insufficient to induce apoptosis of DP thymocytes and further suggest that TCR stimulationactivates a CsA-sensitive protective pathway that interferes with signaling eventsleading to apoptosis in DP thymocytes.

Autor: Heather L. Poetschke, David B. Klug, Dawn Walker, and Ellen R. Richie



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