Models of Anergy in the Human Jurkat T Cell Line

Abstract

We investigated two model systems to study anergy in a human T cell line. OKT3 or calcium ionophore stimulation of Jurkat cells, in the absence of costimulation, resulted in a steep reduction in the transcription and secretion of IL-2 in response to subsequent stimulation via CD3 and CD28. Treatment of anergic Jurkat cells with the combination of the phorbol ester, PMA, and ionomycin restored IL-2 production in cells rendered anergic by both mechanisms. However, hydrogen peroxide, which also stimulates kinases downstream of the proposed block that occurs in anergic murine cells, did not reverse the anergic state of these cells induced by either stimulus. The cause of unresponsiveness in these two models was found to differ. OKT3-induced anergy resulted in a substantial down-regulation of the CD3 on these cells. In contrast, anergy induced by treatment with a calcium ionophore did not result in CD3 down-regulation. These data indicate that the Jurkat cell line may serve as a suitable model for studying anergy in human T cells; however, the mechanism by which anergy is induced may vary dramatically in response to these two commonly used anergy-inducing strategies. Understanding the similarities and differences between these two models of anergy may lead to a better overall understanding of the anergic state of the T cell.