Heterologous immunity provides a potent barrier to transplantation tolerance
J. Clin. Invest. Andrew B. Adams, et al. 111:1887 doi:10.1172/JCI17477 [Go to this article.]

Figure 4
DSG and costimulation blockade synergistically inhibit memory cells. Both alloreactive and virus-specific memory cell responses were analyzed. (a) Skin graft survival of mice that had previously (1 week earlier) received T cells from sensitized congenic mice and were treated with either the tolerance induction protocol alone or in combination with various agents. The combination of DSG and costimulatory blockade promoted tolerance of donor-specific memory cells (n = 5; MST, 100 days; filled squares). The costimulation blockade tolerance regimen given alone (n = 5, open squares) or in combination with other agents, including rapamycin (n = 5, filled triangles), anti-CD25 (n = 5, open triangles), and anti-γ_c (n = 5, filled diamonds) failed to inhibit memory-dependent rejection. Two additional experiments demonstrated similar results. (b) LCMV-immune mice were rechallenged with LCMV clone 13 and treated with costimulation blockade (costim), DSG, or the combination of costimulation blockade and DSG. Five days after rechallenge, CD8⁺ (class I restricted NP396-404 and GP276-286) and CD4⁺ (class II restricted P13 GP60-80) responses were analyzed. The combination of costimulatory blockade and DSG synergistically inhibited LCMV-specific CD8⁺ memory T cells (*P < 0.01). No tx, no treatment; immune no rechall, immune mouse without viral rechallenge.