Why do you think your paper is highly cited?

Timing is everything. We published just when regulatory T cells were gaining a great deal of credibility and interest in the community. The data were compelling for their role and the model was put on the cover of the journal.

  Does it describe a new discovery or new methodology that's useful to others?

It demonstrated the important biological role of a controversial subset of T cells in autoimmunity.

  Could you summarize the significance of your paper in layman's terms?

In recent years, immunologists have begun to appreciate the critical role of negative immune regulation in the control of the adaptive immune response and autoimmunity. Historically, certain molecules, like the CD28 co-stimulatory receptor, have been implicated as positive regulators while other cell surface proteins, like CTLA-4, have been shown to negatively regulate T cell responses. In our work, we studied the role of these critical pathways in immune regulation focusing on a novel T cell subset that control autoimmune disease in an animal model of spontaneous diabetes. The work highlighted the complexity of these pathways, showing that the so-called co-stimulatory pathway mediated by CD28 was critical for the development of the regulator T cells such that in the absence of these pathways the cells had reduced survival resulting in exacerbation of auto-immunity. In addition, we were the first to show that these CD25+CD4+ cells express CTLA-4 that has been subsequently reported to be a critical positive regulatory of their activity. Thus, the study emphasized the dynamic regulation of immunity and the potential role of these cellular and molecular pathways in immune tolerance and disease.

Jeffrey A. Bluestone
UCSF Diabetes Center
University of California, San Francisco
513 Parnassus Ave.
Box 0540 - HSW Room 1114
San Francisco, CA 94143-0540