Cutting edge : cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells

Chun Jing Wang, Rupert Kenefeck, Lukasz Wardzinski, Kesley Attridge, Claire Manzotti, Emily M. Schmidt, Omar S. Qureshi, David M. Sansom, Lucy S.K. Walker

Research output: Contribution to journalArticlepeer-review


The CTLA-4 pathway is a key regulator of T cell activation and a critical failsafe against autoimmunity. Although early models postulated that CTLA-4 transduced a negative signal, in vivo evidence suggests that CTLA-4 functions in a cell-extrinsic manner. That multiple cell-intrinsic mechanisms have been attributed to CTLA-4, yet its function in vivo appears to be cell-extrinsic, has been an ongoing paradox in the field. Although CTLA-4 expressed on conventional T cells (Tconv) can mediate inhibitory function, it is unclear why this fails to manifest as an intrinsic effect. In this study, we show that Tconv-expressed CTLA-4 can function in a cell-extrinsic manner in vivo. CTLA-4(+/+) T cells, from DO11/rag(-/-) mice that lack regulatory T cells, were able to regulate the response of CTLA-4(-/-) T cells in cotransfer experiments. This observation provides a potential resolution to the above paradox and suggests CTLA-4 function on both Tconv and regulatory T cells can be achieved through cell-extrinsic mechanisms.

Original languageEnglish
Pages (from-to)1118-1122
Number of pages5
JournalJournal of Immunology
Issue number3
Early online date19 Jul 2012
Publication statusPublished - 1 Aug 2012


  • adoptivetransfer
  • bone marrow transplantation
  • CTLA-4 antigen
  • growth Inhibitors
  • immune tolerance
  • cellular immunity
  • radiation Chimera
  • T-lymphocyte subsets
  • regulatory T-lymphocytes


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