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Cutting Edge: The SLAM Family Receptor Ly108 Controls T Cell and Neutrophil Functions ¹

Duncan Howie^2,*, F. Stephen Laroux^*, Massimo Morra^*, Abhay R. Satoskar, Lucia E. Rosas, William A. Faubion^3,*, Aimee Julien^*, Svend Rietdijk^*, Anthony J. Coyle, Christopher Fraser and Cox Terhorst^*

^* Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215; Department of Microbiology, Ohio State University, Cleveland, OH 43210; MedImmune Inc., Gaithersberg, MD 20878; and Millenium Pharmaceuticals, Cambridge, MA 02139

Ly108, a glycoprotein of the signaling lymphocytic activation molecule family of cell surface receptors expressed by T, B, NK, and APCs has been shown to have a role in NK cell cytotoxicity and T cell cytokine responses. In this study, we describe that CD4⁺ T cells from mice with a targeted disruption of exons 2 and 3 of Ly108 (Ly108^E2+3) produce significantly less IL-4 than wild-type CD4⁺ cells, as judged by in vitro assays and by in vivo responses to cutaneous infection with Leishmania mexicana. Surprisingly, neutrophil functions are controlled by Ly108. Ly108^E2+3 mice are highly susceptible to infection with Salmonella typhimurium, bactericidal activity of Ly108^E2+3 neutrophils is defective, and their production of IL-6, IL-12, and TNF- is increased. The aberrant bactericidal activity by Ly108^E2+3 neutrophils is a consequence of severely reduced production of reactive oxygen species following phagocytosis of bacteria. Thus, Ly108 serves as a regulator of both innate and adaptive immune responses.

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