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In Vitro Negative Selection of Viral Superantigen-Reactive Thymocytes by Thymic Dendritic Cells

Isabel Ferrero, Fabienne Anjuère, H. Robson MacDonald, and Carlos Ardavín

From the Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain, and the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.

Intrathymic expression of endogenous mouse mammary tumor virus (MMTV)-encoded superantigens (SAg) induces the clonal deletion of T cells bearing SAg-reactive T-cell receptor (TCR) Vbeta elements. However, the identity of the thymic antigen-presenting cells (APC) involved in the induction of SAg tolerance remains to be defined. We have analyzed the potential of dendritic cells (DC) to mediate the clonal deletion of Mtv-7-reactive TCR alpha beta P14 transgenic thymocytes in an in vitro assay. Our results show that both thymic and splenic DC induced the deletion of TCR transgenic double positive (DP) thymocytes. DC appear to be more efficient than splenic B cells as negatively selecting APC in this experimental system. Interestingly, thymic and splenic DC display a differential ability to induce CD4+SP thymocyte proliferation. These observations suggest that thymic DC may have an important role in the induction of SAg tolerance in vivo.

Blood, Vol. 90 No. 5 (September 1), 1997: pp. 1943-1951
© 1997 by The American Society of Hematology.


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