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Self Nonself. 2010 Apr;1(2):77-88. Epub 2010 Feb 16.

Co-inhibitory molecules: Controlling the effectors or controlling the controllers?

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  • 1Department of Surgery; Alberta Diabetes Institute; University of Alberta; Edmonton, Alberta Canada.


Nearly forty years ago the concept was proposed that lymphocytes are negatively regulated by what are now called co-inhibitory signals. Nevertheless, it is only the more recent identification of numerous co-inhibitors and their critical functions that has brought co-inhibition to the forefront of immunologic research. Although co-inhibitory signals have been considered to directly regulate conventional T cells, more recent data has indicated a convergence between co-inhibitory signals and the other major negative control mechanism in the periphery that is mediated by regulatory T cells. Furthermore, it is now clear that lymphocytes are not the sole domain of co-inhibitory signals, as cells of the innate immune system, themselves controllers of immunity, are regulated by co-inhibitors they express. Thus, in order to better understand negative regulation in the periphery and apply this knowledge to the treatment of disease, a major focus for the future should be the definition of the conditions where co-inhibition controls effector cells intrinsically versus extrinsically (via regulatory or innate cells).

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