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Jakmip1 Is Expressed upon T Cell Differentiation and Has an Inhibitory Function in Cytotoxic T Lymphocytes¹

Valentina Libri^*,, Dörte Schulte^*, Amber van Stijn, Josiane Ragimbeau^*, Lars Rogge and Sandra Pellegrini^2,*

^* Cytokine Signaling Unit and Immunoregulation Group, Department of Immunology, Centre National de la Recherche Scientifique Unité de Recherche Associée 1961, Institut Pasteur, 75724 Paris, France; Department of Immunology and Molecular Pathology, University College London, London, United Kingdom; Department of Experimental Immunology and Department of Internal Medicine, Division of Nephrology, Academic Medical Center, Amsterdam, the Netherlands

Jakmip1 belongs to a family of three related genes encoding proteins rich in coiled-coils. Jakmip1 is expressed predominantly in neuronal and lymphoid cells and colocalizes with microtubules. We have studied the expression of Jakmip1 mRNA and protein in distinct subsets of human primary lymphocytes. Jakmip1 is absent in naive CD8⁺ and CD4⁺ T lymphocytes from peripheral blood but is highly expressed in Ag-experienced T cells. In cord blood T lymphocytes, induction of Jakmip1 occurs upon TCR/CD28 stimulation and parallels induction of effector proteins, such as granzyme B and perforin. Further analysis of CD8⁺ and CD4⁺ T cell subsets showed a higher expression of Jakmip1 in the effector CCR7^– and CD27^– T cell subpopulations. In a gene expression follow-up of the development of CMV-specific CD8⁺ response, Jakmip1 emerged as one of the most highly up-regulated genes from primary infection to latent stage. To investigate the relationship between Jakmip1 and effector function, we monitored cytotoxicity of primary CD8⁺ T cells silenced for Jakmip1 or transduced with the full-length protein or the N-terminal region. Our findings point to Jakmip1 being a novel effector memory gene restraining T cell-mediated cytotoxicity.

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 Institut Pasteur, Centre National de la Recherche Scientifique, Association pour la Recherche sur le Cancer (to S.P.). V.L. was supported by the Fondazione Italiana per la Ricerca sul Cancro and the French Ministry of Foreign Affairs; A.v.S. by the Dutch Kidney Foundation Grant C0.2034. L.R. was supported by funding under the Sixth Research Framework Programme of the European Union, Project MUGEN (MUGEN LSHB-CT-2005-005203).

² Address correspondence and reprint requests to Dr. S. Pellegrini, Cytokine Signaling Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris, cedex 15, France. E-mail address: pellegri{at}pasteur.fr

³ Abbreviations used in this paper: T_N, naive T lymphocyte; T_CM, central memory T lymphocyte; T_EM, effector memory T lymphocyte; T_EMRA effector memory RA T lymphocyte; siRNA, short interfering RNA; RT-qPCR, real-time quantitative PCR.