Antibody to the dendritic cell surface activation antigen CD83 prevents acute graft-versus-host disease

RA83 treatment of hu-SCID mice did not impair subsequent in vitro induction of antiviral and allo antileukemic cytotoxic T cell effectors from cells recovered from hu-SCID mice. 10-d posttransplant hu-SCID mice treated with 125 μg RA83 (n = 19 mice; GVHD score = 0.5 on day 9) or RAneg (n = 5 mice; GVHD score = 3.25 on day 9) were killed, cells from spleen, bone marrow, and peritoneal washings were combined, and human leukocytes recovered (see Materials and methods). These cells and, as a control, an equal number of freshly thawed PBMC from the same donor, were stimulated in vitro with irradiated autologous PBMC plus either peptide antigen or irradiated leukemic cell lines. After two rounds of stimulation, T cell–mediated lysis of FMP peptide-loaded T2 cells (a), U937 (c), Raji (d), Nalm6 (e), and ALL-19 (a human primary ALL passaged in NOD-SCID mice [reference 40]; f) leukemic cell lines was measured by ⁵¹Cr release assay. Specific killing of T2 cells loaded with peptide from the naive melanoma-associated antigen Mart1 was assayed after four rounds of stimulation (b). (▴, RA83; ▾, RAneg; ▪, freshly thawed donor PBMC). Dashed lines in a and b show minimal lysis of T2 cells loaded with irrelevant HIV peptide (RA83, P < 0.01 for FMP and 0.001 for Mart1 compared with HIV). Data are from one representative experiment of three using one HLA-A*0201+ PBMC donor.