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Recombinant Ad35 adenoviral proteins as potent modulators of human T‐cell activation
Author(s) -
Hay Joanne,
Carter Darrick,
Lieber André,
Astier Anne L.
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12391
Subject(s) - t cell , microbiology and biotechnology , immune system , biology , secretion , cytokine , cell , receptor , recombinant dna , cell growth , immunology , biochemistry , gene
Summary The protein CD 46 protects cells from complement attack by regulating cleavage of C3b and C3d. CD 46 also regulates the adaptive immune response by controlling T‐cell activation and differentiation. Co‐engagement of the T‐cell receptor and CD 46 notably drives T‐cell differentiation by switching production of interferon‐ γ to secretion of anti‐inflammatory interleukin‐10. This regulatory pathway is altered in several chronic inflammatory diseases, highlighting its key role for immune homeostasis. The manipulation of the CD 46 pathway may therefore provide a powerful means to regulate immune responses. Herein, we investigated the effect of recombinant proteins derived from the fibre knob of the adenovirus serotype 35 (Ad35) that uses CD 46 as its entry receptor, on human T‐cell activation. We compared the effects of Ad35K++, engineered to exhibit enhanced affinity to CD 46, and of Ad35K−, mutated in the binding site for CD 46. Ad35K++ profoundly affects T‐cell activation by decreasing the levels of CD 46 at the surface of primary T cells, and impairing T‐cell co‐activation, shown by decreased CD 25 expression, reduced proliferation and lower secretion of interleukin‐10 and interferon‐ γ . In contrast, Ad35K− acts a potent co‐activator of T cells, enhancing T‐cell proliferation and cytokine production. These data show that recombinant Ad35 proteins are potent modulators of human T‐cell activation, and support their further development as potential drugs targeting T‐cell responses.