Cutting edge: The SLAM family receptor Ly108 controls T cell and neutrophil functions

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^ΔE2+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 ^ΔE2+3 mice are highly susceptible to infection with Salmonella typhimurium, bactericidal activity of Ly108^ΔE2+3 neutrophils is defective, and their production of IL-6, IL-12, and TNF-α is increased. The aberrant bactericidal activity by Ly108^ΔE2+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.