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

Abstract

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.