CD28-B7 interactions function to co-stimulate clonal deletion of double-positive thymocytes

International Immunology
D Amsen, A M Kruisbeek

Abstract

Negative selection of thymocytes only occurs if next to signals through the TCR, additional antigen-presenting cell (APC)-derived signals are also provided. It has been unclear which molecular interactions lead to the generation of these signals. In particular, the involvement of CD28 and its ligands B7-1 and B7-2 has been controversial. In the present study, we re-address this issue and first confirm that cross-linking CD28 molecules on thymocytes can indeed complement TCR-derived signals for induction of deletion upon TCR engagement with antibodies. Furthermore, we extend these findings by documenting that also peptide agonist-induced deletion can be co-stimulated by antibody-mediated engagement of CD28. Additionally, blocking B7-1 or B7-2 reduces negative selection induced by both anti-CD3 and peptide agonist in suspension cultures and in fetal thymic organ culture. At the same time, prominent co-stimulation of TCR-induced deletion could be provided by a B7-negative cell line. Together these results definitively demonstrate that CD28-B7 interactions can function to co-stimulate induction of clonal deletion, while yet to be identified B7-independent co-stimulatory signals can fulfil this function as well.

Citations

Apr 17, 2002·The Journal of Experimental Medicine·Jian-Xin GaoYang Liu
Mar 30, 2005·The Journal of Experimental Medicine·Connie L SommersLawrence E Samelson
Dec 16, 1998·Immunological Reviews·D Amsen, A M Kruisbeek
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Jan 20, 1999·Proceedings of the National Academy of Sciences of the United States of America·D AmsenA M Kruisbeek
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