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T cell vaccination (TCV) activates Tregs of 2 kinds: anti-idiotypic (anti-id) and anti-ergotypic (anti-erg). These regulators furnish a useful view of the physiology of T cell regulation of the immune response. Anti-id Tregs recognize specific effector clones by their unique TCR CDR3 peptides; anti-id networks of CD4+ and CD8+ Tregs have been described in detail. Here we shall focus on anti-erg T regulators. Anti-erg T cells, unlike anti-id T cells, do not recognize the clonal identity of effector T cells; rather, anti-erg T cells recognize the state of activation of target effector T cells, irrespective of their TCR specificity. We consider several features of anti-erg T cells: their ontogeny, subset markers, and target ergotope molecules; mechanisms by which they regulate other T cells; mechanisms by which they get regulated; and therapeutic prospects for anti-erg upregulation and downregulation.

Tregs in T cell vaccination: exploring the regulation of regulation