Editors' ChoiceImmunology

Linking Immune Responses by CD46

Science's STKE  09 Jul 2002:
Vol. 2002, Issue 140, pp. tw248-TW248
DOI: 10.1126/stke.2002.140.tw248

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]