T cell signals in tolerance.

In contact sensitivity (and other forms of T cell sensitivities), T cell activation and priming of the system requires at least two signals. Signal 1 includes specific antigen and signal 2 is a nonspecific stimulus. Ordinarily, the signals are invoked in an associative manner, but they can be delivered separately. The physiocochemical nature of the antigen and the manner of host processing are critical to the delivery of signal 2. Tolerance in unprimed systems is induced by the presentation of signal 1 (antigen) in forms and by routes that do not activate signal 2. This seems to invoke suppressor mechanisms and to directly inactivate TDH cells. In primed systems where contact sensitivity is present, signals 1 and 2 boost the response. In primed systems, "off signals" (desensitization) may be provided by some anti-id antibodies, which act by stimulating suppressor mechanisms that finally work to down regulate TDH. Antigen alone (signal 1) also appears to be capable of directly down regulating TDH, but so far it has not proved a powerful tool in desensitizing primed T cells.