Treg cells results in the destruction of activated, MBP-reactive Th1 clonotypes, causing a ‘global’deviation of the immune response and protection from EAE (V. Kumar, La Jolla, CA, USA). In confirmation of the animal studies, MBP-reactive T cells have been shown also to disappear following TCV in humans. Interestingly, CD4+ Treg cells must secrete pro-inflammatory cytokines, for example, interferon γ (IFN-γ), for effective TCR-based regulation (V. Kumar). Accordingly, Th1 clones, but not Th2 clones, can be used to vaccinate successfully against EAE. Consistent with this, a CD8+ Treg hybridoma has been shown to recognize the Th1 version but not the Th2 version of a clone (H. Jiang).

These studies suggest that, contrary to some expectations, T-cell lines used for vaccination should be of the Th1 phenotype. Thus, pro-inflammatory cytokines might be required for the effective recruitment of CD8+ T cells. Furthermore, it appears that the display of TCR-derived-peptide–MHC complexes on a professional Ag-presenting cell (APC), following uptake of an apoptotic T cell or its contents, is crucial for the priming of Treg populations. Because Th2 cells are less susceptible to apoptosis than Th1 cells, vaccination with Th2 cells might not load APCs for the effective priming of Treg cells. Alternatively, activated T cells displaying the TCR-derived-peptide–MHC complexes on their cell surface could directly prime CD8+ Treg cells. An important issue in TCV is identifying the relevant T-cell clones or