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Th17 Cells Exhibit a Distinct Calcium Profile from Th1 and Th2 Cells and Have Th1-Like Motility and NF-AT Nuclear Localization¹

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

Helper T cell subsets have evolved to respond to different pathogens, and upon activation secrete distinct sets of cytokines. The discovery and identification of Th17 cells, which develop via a unique lineage from Th1 and Th2 cells, have provided new insights into aspects of immune regulation and host defense that were previously unclear. A key early signaling event upon Ag recognition is elevation of intracellular free Ca²⁺, and cytokine expression can be differentially induced depending on the duration, amplitude, and pattern of Ca²⁺ signaling. Th1 and Th2 cells can be distinguished by their Ca²⁺ profiles, and we provide in this study the first report regarding Ca²⁺ signaling in Th17 cells. Th17 cells have a distinct Ca²⁺ signaling profile from Th1 and Th2 cells with intermediate sustained Ca²⁺ levels and increased oscillations compared with Th2 cells. Elevated intracellular Ca²⁺ has been shown to inhibit T cell motility, and we observed that Th17 cells, like Th1 cells, are less motile than Th2 cells. Analysis of NF-AT nuclear localization revealed that Th1 and Th17 cells have significantly higher levels at later time points compared with Th2 cells. Thus, these findings show that Th17 cells, in addition to their distinct cytokine response from Th1 and Th2 cells, display unique patterns of intracellular Ca²⁺ signaling and Th1-like motility behavior and nuclear localization of NF-AT.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the National Institutes of Health, and K.S.W. was supported by a National Institutes of Health training grant.

² Address correspondence and reprint requests to Dr. Paul M. Allen, Washington University School of Medicine, Department of Pathology and Immunology, 660 South Euclid Avenue, Campus Box 8118, St. Louis, MO 63110. E-mail address: pallen{at}wustl.edu

³ Abbreviations used in this paper: [Ca²⁺]_i, intracellular free calcium; PLC1, phospholipase C1; Hb, hemoglobin.