Abstract
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.
Publication DOI: | https://doi.org/10.4049/jimmunol.1200972 |
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Divisions: | Life & Health Sciences |
Uncontrolled Keywords: | adoptivetransfer,bone marrow transplantation,CTLA-4 antigen,growth Inhibitors,immune tolerance,cellular immunity,radiation Chimera,T-lymphocyte subsets,regulatory T-lymphocytes |
Published Date: | 2012-08-01 |
Authors: |
Wang, Chun Jing
Kenefeck, Rupert Wardzinski, Lukasz Attridge, Kesley ( ![]() Manzotti, Claire Schmidt, Emily M. Qureshi, Omar S. Sansom, David M. Walker, Lucy S.K. |