Termination of Tolerance

If tolerance depends on maintenance of a state of anergy, several possible scenarios could explain the termination of tolerance:

1. Clonal regeneration. Because new B lymphocytes are constantly produced from stem cells, if a tolerogenic dose of antigen is not maintained, the immune system will eventually replace aging, tolerant cells with young, nontolerant cells and recover the ability to mount an immune response.

2. Cross-immunization. Exposure to an antigen that cross-reacts with a tolerogen may induce activation of T-helper (Th) lymphocytes specific for the cross-reacting antigen and provide autoreactive B lymphocytes with the co-stimulatory signals necessary to initiate a response against the tolerogen.

3. Co-stimulation of anergic clones. It was discussed previously that anergy may be the result of incomplete stimulation of T lymphocytes. Thus, it can be postulated that proper stimulation of T lymphocytes by reestablishing the co-stimulatory pathway can terminate anergy and initiate the autoreactive process (Silverstein and Rose 2000).

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