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International Immunology Advance Access published online on August 16, 2004
International Immunology, doi:10.1093/intimm/dxh141
© 2004 by The Japanese Society for Immunology
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Received May 4, 2004
Accepted July 9, 2004

Article

A new role for CD28 in the survival of autoreactive T cells in the periphery after chronic exposure to autoantigen

Jian-Xin Gao 1, Xing Chang 1, Xincheng Zheng 1, Jing Wen 1, Lijie Yin 1, Peishuang Du 1, Pan Zheng 1, Yang Liu 1*

1 Division of Cancer Immunology, Department of Pathology, Ohio State University Medical Center, Columbus, OH 43210, USA

* To whom correspondence should be addressed. E-mail: liu-3{at}medctr.osu.edu.


  Abstract

Recent work demonstrates that costimulatory molecules play a critical role for clonal deletion of autoreactive T cells in the thymus. The role of CD28 in the survival of autoreactive T cells in the periphery, however, has not been reported. Here we demonstrate that while mutation of the CD28 gene consistently increased the burden of autoreactive T cells in the thymus, such an increase was not always found in the periphery, as the CD28(-/-) autoreactive T cells disappeared in the spleen over a period between 4 and 10 weeks. The disappearance of autoreactive T cells associates with a diminished induction of Bcl-2 protein by the self antigen and an increased proportion of apoptotic cells in the periphery. Moreover, the elimination of autoreactive T cells in the periphery requires chronic stimulation by the self antigen, as adoptive transfer analysis revealed no enhancement of apoptosis in CD28(-/-) T cells in antigen-bearing hosts over a 3 day period. Thus, CD28 plays a significant role in both clonal deletion and survival of autoreactive T cells after chronic exposure to autoantigens, resulting in opposite effects on the burden of autoreactive T cells.

Keywords: cell-surface molecules; repertoire development; T lymphocyte.
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