Recipient elimination of allogeneic lymphoid cells: donor CD4(+) cells are effective alloantigen-presenting cells

The encounter with allogeneic major histocompatibility complex (MHC) molecules expressed on donor leukocytes during transfusion of blood products has been shown to impact the recipient's immune responses in a number of settings. To better understand the responses induced by the transfer of allogeneic cells, a murine model was used to characterize the recipient responses that control the fate of the allogeneic lymphoid cells. Recipient CD8(+) cells could rapidly eliminate a large number of donor cells within 3 days after injection. When elimination responses were studied in the absence of CD8(+) cells, it was found that alloantibody production was the secondary elimination mechanism. Optimal recipient CD8(+) and B cell responses in this model required help from CD4(+) cells that could be provided by 3 different pathways. Although recipient CD4(+) cells could provide help when activated by direct recognition of allogeneic MHC class II molecules expressed on donor cells or by indirect recognition of processed alloantigen presented on recipient antigen-presenting cells (APCs), the most rapid recipient responses were generated by help provided by donor CD4(+) cells. Purified donor CD4(+) cells were also able to induce these rapid responses, indicating that activated donor CD4(+) cells expressing allogeneic MHC molecules were able to effectively stimulate responses by both recipient CD8(+) and B cells.