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Cutting Edge: Inhibition of T Cell Activation by TIM-2¹

Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261

T cell Ig and mucin domain protein 2 (TIM-2) has been shown to regulate T cell activation in vitro and T cell-mediated disease in vivo. However, it is still not clear whether TIM-2 acts mainly to augment T cell function or to inhibit it. We have directly examined the function of TIM-2 in murine and human T cell lines. Our results indicate that expression of TIM-2 significantly impairs the induction of NFAT and AP-1 transcriptional reporters by not only TCR ligation but also by the pharmacological stimuli PMA and ionomycin. This does not appear to be due to a general effect on cell viability, and the block in NFAT activation can be bypassed by expression of activated alleles of Ras or calcineurin, or MEK kinase, in the case of AP-1. Thus, our data are consistent with a model whereby TIM-2 inhibits T cell activation.

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 start-up funds from the University of Pittsburgh School of Medicine (to L.P.K.).

² J.E.K. and A.J.D. contributed equally.

³ Address correspondence and reprint requests to Dr. Lawrence P. Kane, Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261. E-mail address: lkane{at}pitt.edu

⁴ Abbreviations used in this paper: TIM, T cell Ig and mucin domain; MEKK, MEK kinase; PKC, protein kinase C.

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