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Title

CD46-Mediated costimulation induces a Th1-biased response and enhances early TCR/CD3 signaling in human CD4+ T lymphocytes

AuthorsSánchez, Alejandra; Feito, María José; Rojo, José María
KeywordsComplement
Costimulation
Th1
Th2 cells
Issue DateSep-2004
PublisherWiley-VCH
CitationEuropean Journal of Immunology 34(9):2439-2448(2004)
AbstractThe role of membrane cofactor protein (MCP, CD46) on human T cell activation has been analyzed. Coligation of CD3 and CD46 in the presence of PMA or CD28 costimuli enhanced IL-2, IFN-γ, or IL-10 secretion by CD4+ T lymphocytes. The effect of CD46 on IL-10 secretion did not require additional costimuli like anti-CD28 antibodies or phorbol esters. CD46 also enhanced IL-2 or IFN-γ secretion by CD4+ blasts. In contrast, IL-5 secretion was inhibited upon CD46-CD3 coligation, in all the cells analyzed. These effects were independent of IL-12 and suggest that CD46 costimulation promotes a Th1-biased response in human CD4+ T lymphocytes. CD46 enhanced TCR/CD3-induced tyrosine phosphorylation of CD3ζ and ZAP-70, as well as the activation of the ERK, JNK, and p38, but did not modify intracellular calcium. The effect of specific inhibitors shows that enhanced ERK activation contributes to augmented IFN-γ and lower IL-5 secretion and, consequently, to the Th1 bias. Cross-linking CD46 alone induced weak tyrosine phosphorylation of CD3ζ and ZAP-70. However, CD46 cross-linking by itself did not induce cell proliferation or lymphokine secretion, and pretreatment of CD4+ T lymphocytes with anti-CD46 antibodies did not significantly alter TCR/CD3 activation
Description10 páginas, 8 figuras -- PAGS nros. 2439-2448
Publisher version (URL)http://dx.doi.org/10.1002/eji.200324259
URIhttp://hdl.handle.net/10261/65995
DOI10.1002/eji.200324259
ISSN0014-2980
E-ISSN1521-4141
Appears in Collections:(CIB) Artículos
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