Requirement for a complex array of costimulators in the negative selection of autoreactive thymocytes in vivo

The Journal of Immunology : Official Journal of the American Association of Immunologists
R Li, D M Page

Abstract

Autoreactive thymocytes can be deleted at an immature stage of their development by Ag-induced apoptosis or negative selection. In addition to Ag, negative selection also requires costimulatory signals from APC. We recently used a fetal thymus organ culture system to show that CD5, CD28, and TNF cooperatively regulate deletion of autoreactive thymocytes. Although these experiments provided strong evidence for the action of several costimulators in negative selection, we wished to demonstrate a role for these molecules in a physiologically natural model where thymocytes are deleted in vivo by endogenously expressed AGS: Accordingly, we examined thymocyte deletion in costimulator-null mice in three models of autoantigen-induced negative selection. We compared CD5(-/-) CD28(-/-) mice to CD40L(-/-) mice, which exhibited a profound block in negative selection in all three systems. Surprisingly, only one of the three models revealed a requirement for the CD5 and CD28 costimulators in autoantigen-induced deletion. These results suggest that an extraordinarily complex array of costimulators is involved in negative selection. We predict that different sets of costimulators will be required depending on the timing of negative selection, ...Continue Reading

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Citations

Dec 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hyung J ChoJennifer A Punt
Jul 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shin-Young NaUrsula Bommhardt
May 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erin JanssenWeiguo Zhang
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