Costimulation blockade in combination with IL-2 permits regulatory T cell sparing immunomodulation that inhibits autoimmunity.
- Resource Type
- Academic Journal
- Authors
- Wang CJ; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Petersone L; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Edner NM; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Heuts F; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Ovcinnikovs V; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Ntavli E; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Kogimtzis A; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Fabri A; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Elfaki Y; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Houghton LP; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Hosse RJ; Roche Innovation Center Zurich, Roche Pharma Research & Early Development (pRED), Schlieren, Switzerland.; Schubert DA; Roche Innovation Center Basel, Roche Pharma Research & Early Development (pRED), Basel, Switzerland.; Frei AP; Roche Innovation Center Basel, Roche Pharma Research & Early Development (pRED), Basel, Switzerland.; Ross EM; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK.; Walker LSK; Institute of Immunity & Transplantation, Pears Building, University College London Division of Infection & Immunity, London, UK. lucy.walker@ucl.ac.uk.
- Source
- Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
- Subject
- Language
- English
Blockade of CD28 costimulation with CTLA-4-Ig/Abatacept is used to dampen effector T cell responses in autoimmune and transplantation settings. However, a significant drawback of this approach is impaired regulatory T cell homeostasis that requires CD28 signaling. Therefore, strategies that restrict the effects of costimulation blockade to effector T cells would be advantageous. Here we probe the relative roles of CD28 and IL-2 in maintaining Treg. We find provision of IL-2 counteracts the regulatory T cell loss induced by costimulation blockade while minimally affecting the conventional T cell compartment. These data suggest that combining costimulation blockade with IL-2 treatment may selectively impair effector T cell responses while maintaining regulatory T cells. Using a mouse model of autoimmune diabetes, we show combined therapy supports regulatory T cell homeostasis and protects from disease. These findings are recapitulated in humanised mice using clinically relevant reagents and provide an exemplar for rational use of a second immunotherapy to offset known limitations of the first.
(© 2022. The Author(s).)