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 alphabeta 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.