Macrophage Suppression of T Cell Activation: A Potential Mechanism of Peripheral Tolerance

The mechanisms of induction and maintenance of tolerance in self-reactive T cells in the periphery are poorly understood. Current models assume that successful T cell activation only occurs if ligation of the T cell receptor (signal 1) by antigen presenting cells (APCs) is accompanied by a costimulatory signal (signal 2), and that signal 1 in the absence of signal 2 is either ignored or is tolerizing. However, there is also evidence for the existence of macrophages (M phi) capable of suppressing T cell activation both in vitro and in vivo. The possibility of a more actively induced tolerance exists, in which the M phi itself responds to T cell-mediated signals in a tolerogenic fashion. This would help to resolve the paradox that tissue M phi, which act as scavengers of self-antigen, can also act as professional APCs. The ability of tissue macrophages to actively suppress T cells would further underscore the importance of the innate immune system in regulating adaptive immune responses.