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

Wang, Chun Jing, Kenefeck, Rupert, Wardzinski, Lukasz, Attridge, Kesley, Manzotti, Claire, Schmidt, Emily M., Qureshi, Omar S., Sansom, David M. and Walker, Lucy S.K. (2012). Cutting edge : cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells. Journal of Immunology, 189 (3), pp. 1118-1122.


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:
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 ( 0000-0003-4521-9009)
Manzotti, Claire
Schmidt, Emily M.
Qureshi, Omar S.
Sansom, David M.
Walker, Lucy S.K.


Item under embargo.

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