P59 super(fyn) is Upregulated in Anergic CD8 super(+) T Cells

• Published in: Human immunology Vol. 63; no. 10; pp. 834 - 843
• Main Authors: Welke, J, Zavazava, N
• Format: Journal Article
• Language: English
• Published: 01.10.2002
• ISSN: 0198-8859

The ultimate goal in clinical transplantation is achievement of graft tolerance. Despite long-term immunosuppression, alloantigens on transplants elicit alloresponses that can initiate organ rejection. Acute rejection is mediated by CD8 super(+) cytotoxic T cells, whereas chronic rejection is a result of many factors including non-immunological events. The aim of this study was to examine the molecular requirements of T cell anergy, a cellular state that is an integral component of tolerance in vivo. In vitro, the tolerant state is usually best represented by T cell anergy, which is defined by loss of the ability of T cells to produce and secrete interleukin-2 upon restimulation. In the literature, molecular changes in anergic CD4 super(+) T cells have been studied in great detail, but only little is known about functional and biochemical characteristics of anergic CD8 super(+) T lymphocytes. In this study, we demonstrate, that CD8 super(+) T cells are rendered anergic by TCR stimulation without costimulation. They exhibit impaired interleukin-2 production and tyrosine-phosphorylation, but markedly upregulated p59 super(fyn) expression, which could be shown to be an early event during anergization. Anergic CD8 super(+) T lymphocytes show elevated surface expression of early activation markers as well as costimulatory molecules, especially that of CTLA4. These results, are an important component for the discovery of potential molecular targets, which contribute to the development and maintenance of tolerance.