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There is accumulating evidence that cell surface molecules may be transferred between cells during an encounter. The aim of these experiments was to determine whether transfer of allogeneic material to T cells could influence human alloresponses. CD4+ cells were cocultured with M1 cell (human fibroblast) transfectants expressing HLA-DR1, CD80 and CD86 alone or in combination. Up to 95% of the allogeneic T cells became positive for HLA-DR and the appropriate costimulatory molecules after only 4 h of coculture. The phenomenon required cell contact and cell membrane fluidity because transfer was abolished by transwell separation of the M1 cells and the T cells or by pre-treatment of the APC with paraformaldehyde. Flow cytometric sorting of T cells after coculture and subsequent mixed lymphocyte assays demonstrated that the T cells that had acquired both HLA-DR and costimulatory molecules could act as potent antigen presenting cells. Finally, matured human dendritic cells were also shown to transfer these molecules to CD4+ cells, which could then act as antigen presenting cells for unprimed T cells and for a cell line specific for an HLA-peptide complex acquired from the DCs. Taken together, these data suggest a novel pathway for the amplification of human alloresponses.