Infusion of Anti-B7.1 (CD80) and Anti-B7.2 (CD86) Monoclonal Antibodies Inhibits Murine Graft-Versus-Host Disease Lethality in Part Via Direct Effects on CD4⁺ and CD8⁺ T Cells

Efficient T cell proliferation requires costimulation via CD28/B7 or other pathways. Graft-vs-host disease (GVHD) is caused by activated donor T cells. We have found that the infusion of anti-B7.1 (CD80) + anti-B7.2 (CD86) mAb is effective in eliminating GVHD lethality induced by either CD8⁺ or CD4⁺ T cells. Donor CD4⁺ and CD8⁺ T cell expansion was inhibited by almost 100-fold as measured by enumerating thoracic duct lymphocytes (TDL) obtained early post-transplant. TDL retained anti-host responsiveness indicating that not all T cells were anergic. Although anti-CD80 or anti-CD86 mAb individually were ineffective in preventing CD8⁺ T cell GVHD lethality, each mAb was partially effective in CD4⁺ T cell-mediated GVHD. Because CD80 expression was found to be up-regulated on donor CD4⁺ TDL post-transplant, the GVHD capacity of donor CD4⁺ T cells deficient in CD80 was tested and found to be reduced similarly to that seen with anti-CD80 mAb. These studies demonstrate that anti-CD80 + anti-CD86 mAb infusion is effective in preventing GVHD lethality by inhibiting donor CD4⁺ or CD8⁺ T cell expansion and provide the first evidence that CD80 expression on donor T cells is critical for optimal GVHD lethality.