Reciprocal NFAT1 and NFAT2 Nuclear Localization in CD8 super(+) Anergic T Cells Is Regulated by Suboptimal Calcium Signaling

• Published in: Journal of Immunology Vol. 179; no. 6; pp. 3734 - 3741
• Main Authors: Srinivasan, Mathangi, Frauwirth, Kenneth A
• Format: Journal Article
• Language: English
• Published: 01-09-2007
• ISSN: 0022-1767; 1365-2567

Anergy is an important mechanism of maintaining peripheral immune tolerance. T cells rendered anergic are refractory to further stimulation and are characterized by defective proliferation and IL-2 production. We used a model of in vivo anergy induction in murine CD8 super(+) T cells to analyze the initial signaling events in anergic T cells. Tolerant T cells displayed reduced phospholipase C gamma activation and calcium mobilization, indicating a defect in calcium signaling. This correlated with a block in nuclear localization of NFAT1 in anergic cells. However, we found that stimulation of anergic, but not naive T cells induced nuclear translocation of NFAT2. This suggested that NFAT2 is activated preferentially by reduced calcium signaling, and we confirmed this hypothesis by stimulating naive T cells under conditions of calcium limitation or partial calcineurin inhibition. Thus, our work provides new insight into how T cell stimulation conditions might dictate specific NFAT isoform activation and implicates NFAT2 involvement in the expression of anergy-related genes.