Acquisition of HLA-DR and Costimulatory Molecules by T Cells from Allogeneic Antigen Presenting Cells


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Abstract

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.

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