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-CELLS( AND CD8+ T)

Efficient T cell proliferation requires costimulation via CD28/B7 or o ther pathways. Graft-vs-host disease (GVHD) is caused by activated don or 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 expan sion was inhibited by almost 100-fold as measured by enumerating thora cic duct lymphocytes (TDL) obtained early post-transplant. TDL retaine d anti-host responsiveness indicating that not all T cells were anergi c. Although anti-CD80 or anti-CD86 mAb individually were ineffective i n preventing CD8(+) T cell GVHD lethality, each mAb was partially effe ctive in CD4(+) T cell-mediated GVHD. Because CD80 expression was foun d to be up-regulated on donor CD4(+) TDL post-transplant, the GVHD cap acity of donor CD4(+) T cells deficient in CD80 was tested and found t o be reduced similarly to that seen with anti-CD80 mAb. These studies demonstrate that anti-CD80 + anti-CD86 mAb infusion is effective in pr eventing GVHD lethality by inhibiting donor CD4(+) or CD8(+) T cell ex pansion and provide the first evidence that CD80 expression on donor T cells is critical for optimal GVHD lethality.