Figure 3.

Decreased OT-I T cell expansion in the presence of CTLA-4 Ig/anti-CD154 after priming at low, but not high, antigen-specific precursor frequency. 10⁶ or 10⁷ OT-I T cells (along with 10⁶ OT-II cells) were adoptively transferred into naive B6 recipients that then received an mOVA skin graft. (A) Results showed that mice receiving a low frequency (10⁶) of OT-I T cells were protected from rejection by CTLA-4 Ig/anti-CD154, whereas mice receiving a high frequency (10⁷) rapidly rejected their grafts (P < 0.001). (B) Analysis of the percentage of Thy1.1⁺ CD8⁺ T cells in the DLN revealed that costimulation blockade inhibited the expansion/accumulation of OT-I T cells in mice responding from low frequency, whereas the expansion/accumulation of OT-I cells responding from high frequency was not as potently affected. (C) Absolute numbers of OT-I T cells isolated from the DLN showed a convergence at the peak of expansion at day 10 in both the low and high frequency untreated groups as well as the CTLA-4 Ig/anti-CD154–treated high frequency group. In contrast, the low frequency, CTLA-4 Ig/anti-CD154–treated group exhibited minimal expansion of OT-I T cell numbers. These data are representative examples of four independent experiments, with two to three mice per group, per time point, per experiment.