Co-Stimulatory Blockade of the CD28/CD80-86/CTLA-4 Balance in Transplantation: Impact on Memory T Cells?

Frontiers in Immunology
Simon VilleBernard Vanhove

Abstract

CD28 and CTLA-4 are prototypal co-stimulatory and co-inhibitory cell surface signaling molecules interacting with CD80/86, known to be critical for immune response initiation and regulation, respectively. Initial "bench-to-beside" translation, two decades ago, resulted in the development of CTLA4-Ig, a biologic that targets CD80/86 and prevents T-cell costimulation. In spite of its proven effectiveness in inhibiting allo-immune responses, particularly in murine models, clinical experience in kidney transplantation with belatacept (high-affinity CTLA4-Ig molecule) reveals a high incidence of acute, cell-mediated rejection. Originally, the etiology of belatacept-resistant graft rejection was thought to be heterologous immunity, i.e., the cross-reactivity of the pool of memory T cells from pathogen-specific immune responses with alloantigens. Recently, the standard view that memory T cells arise from effector cells after clonal contraction has been challenged by a "developmental" model, in which less differentiated memory T cells generate effector cells. This review delineates how this shift in paradigm, given the differences in co-stimulatory and co-inhibitory signal depending on the maturation stage, could profoundly affect our ...Continue Reading

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Citations

Jul 13, 2016·European Journal of Immunology·Verena van der Heide, Dirk Homann
Nov 17, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicolas PoirierBernard Vanhove
Apr 20, 2018·Transplantation·Simon Ville, Diego Cantarovich
Apr 1, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Klaus LeyHolger Winkels
Dec 12, 2018·Journal of Leukocyte Biology·Mohammad Afzal Khan, Talal Shamma
Jan 25, 2019·Expert Review of Clinical Immunology·Johan NoblePaolo Malvezzi
Aug 16, 2016·Transplantation·Lionel Rostaing, Paolo Malvezzi
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Nov 21, 2017·Antibodies·Bernard VanhoveGilles Blancho
Sep 23, 2016·Transplantation·Ignacio Anegon, Tuan Huy Nguyen
Jul 10, 2021·Cell·Andreas Wieland, Rafi Ahmed

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Methods Mentioned

BETA
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biopsies

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