MHC class II-mediated antigen presentation by alloreactive rat CD4+ T cells does not induce regulatory properties

Activated CD4+ T cells have the capacity to express major histocompatibility complex (MHC) class II molecules and to present processed antigens to T cells. Because the role of MHC class II positive T cells in allograft rejection is unknown, the purpose of this study was to investigate their function as antigen-presenting cells (APCs) in the allogeneic immune response. For this, alloreactive CD4+ T cells were induced in Lewis rats by immunization with the allogeneic peptide P1. The P1-specific T cells are involved in the rejection of allografts from Wistar Furth rats. With monoclonal antibodies specific for the αβ T-cell receptor (clone R73) and MHC class II molecules (clone Ox6), the presence of antigen-specific T cells, with and without expression of MHC class II molecules, was demonstrated. Concerning their ability to bind these antibodies they were characterized as R73^pos, Ox6^pos and R73^pos, Ox6^neg, respectively. The R73^pos, Ox6^pos T cells loaded with P1 were indeed very effective in restimulating R73^pos, Ox6^neg T cells but not vice versa. Further on, R73^pos, Ox6^pos T cells, but not R73^pos, Ox6^neg T cells, were able to activate naïve allogeneic T cells demonstrating their capacity to express co-stimulatory molecules. In addition, specific mRNA for CD86, MHC class II, and CIITA, the master regulator of MHC class II expression, were detectable in the R73^pos, Ox6^pos T cells only. In conclusion, the R73^pos, Ox6^pos T cells act as professional APCs with the possible biological capability of amplifying the local immune response to the allograft.