Commentary: Regulated equilibrium between opposite signals: a general paradigm for T cell function?

The co-signaling receptors specific for the different members of the B7 molecular family are cell surface glycoproteins that are essential to modulate and tune the TCR-mediated activation of T lymphocytes. The common characteristic is that their function appears to be dependent on the engagement of TCR by antigenic peptides presented in the MHC context by antigen-presenting cells. Interestingly, co-signaling molecules can be distinguished into costimulators and co-inhibitors, the prototype being represented by CD28 and CTLA-4, respectively. In the case of costimulators, the co-signals integrate the signal originated from the TCR resulting in optimal T cell activation (two-signal model). In the case of co-inhibitors, the co-signals would moderate and/or switch off the Ag-dependent T cell activation, thus acting as negative regulators of immune responses. The growing number of novel co-signaling molecules has recently highlighted the need to integrate the two-signal model with the emerging data on the different co-inhibitory interactions. Thus, a model has been proposed based on the idea that the TCR signal alone cannot take a full decision on the nature of the functional outcome following an antigen-specific stimulation and that this final event is governed by the co-signaling molecules.