Linking innate and acquired immunity: divergent role of CD46 cytoplasmic domains in T cell induced inflammation.
CD46 is a widely expressed transmembrane protein that was initially identified as binding and inactivating C3b and C4b complement products. We used mice that were transgenic for one of two human CD46 isoforms that differ in their cytoplasmic domains (termed CD46-1 and CD46-2) to analyze the effect of CD46 stimulation on the immune response. We show here that CD46 can regulate inflammatory responses, either by inhibiting (CD46-1) or increasing (CD46-2) the contact hypersensitivity reaction. We found that engagement of CD46-1 or CD46-2 differentially affected CD8(+) T cell cytotoxicity, CD4(+) T cell proliferation, interleukin 2 (IL-2) and IL-10 production as well as tyrosine phosphorylation of Vav in T lymphocytes. These results indicate that CD46 plays a role in regulating the T cell induced inflammatory reaction and in fine-tuning the cellular immune response by bridging innate and acquired immunity.
Marie
Julien C
JC
INSERM U404, Immunité et Vaccination, CERVI, 21 avenue Tony Garnier, 69365 Lyon, cedex 07, France.
Astier
Anne L
AL
Rivailler
Pierre
P
Rabourdin-Combe
Chantal
C
Wild
T Fabian
TF
Horvat
Branka
B
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D003593:Cytoplasm; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D004139:Dinitrofluorobenzene / Q000009:adverse effects; D004195:Disease Models, Animal; D007110:Immunity, Active / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
D015703:Antigens, CD; D007376:Interleukin-2; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D020033:Protein Isoforms; D016753:Interleukin-10; D004139:Dinitrofluorobenzene