Linking Immune Responses by CD46

Abstract

Marie et al. proposed that the transmembrane glycoprotein CD46, which functions in the activation of complement in the innate immune system, also regulates inflammatory responses of T cells in acquired immunity. CD46 not only binds the C3b and C4b complement products, but is also a receptor for measles and other viruses. Alternative splicing creates several isoforms of CD46, which can contain either a 16-amino acid or a 23-amino acid cytoplasmic tail (called CD46-1 and CD46-2, respectively). The authors made transgenic mice expressing CD46-1 or CD46-2 or both. In vivo, they activated CD46 with measles virus hemagglutinin expressed by inactivated recombinant vesicular stomatitis virus. The two forms of CD46 had opposite effects on T cell function. CD46-2 increased the generation of CD8 + T cells and decreased proliferation of CD4 + cells, leading to less secretion of the anti-inflamatory cytokine interleukin-10 (IL-10). Activation of CD46-1 decreased the proliferation of CD8 + T cells and promoted accumulation of CD4 + cells and IL-10 production. Thus, the relative amounts of expression of the two forms may influence T cell responses in inflammation. The authors suggest that complement activation at sites of inflammation may act through CD46 to modulate T cell-mediated immunity. The actions of CD46 in T cells may also contribute to the problematic immunosuppressive actions of measles virus. J. C. Marie, A. L. Astier, P. Rivailler, C. Rabourdin-Combe, T. F. Wild, B. Horvat, Linking innate and acquired immunity: Divergent role of CD46 cytoplasmic domains in T cell-induced inflammation. Nat. Immun. 3 , 659-666 (2002). [Online Journal]