Figure 2.

(a) A model for T-cell receptor (TCR)-dependent regulation via dendritic cell–T-cell interactions. Regulatory T (Treg) cells may function by means of a negative feedback loop controlling expression of CD80/CD86 on the dendritic cell surface, by analogy with positive feedback providing helper function via CD40 ligand–CD40 interactions with the dendritic cells. (b) A model illustrating how Treg-mediated control of CD80/CD86 expression may control the threshold of antigen recognition, crucial for preventing the activation of low-avidity self-reactive T cells that are below the cut-off imposed during thymic selection (B. Fazekas de St Groth, unpublished data). Treg cells stimulated during high-affinity responses to microbes would increase the threshold (indicated by the green line) by reducing dendritic cell expression of costimulatory molecules. Conversely, in the absence of strong Treg-cell activity, the threshold of self-antigen recognition may drop below the thymic cut-off (indicated by the black line), allowing activation of low avidity anti-self T cells.