Dynamic Expression of Qa-2 during Acute Graft Rejection

Human leukocyte antigen (HLA)-G exhibits immunotolerogenicity and is related to allograft acceptance. Qa-2 is the murine homolog of HLA-G; it has structure and functions similar to those of HLA-G. We investigated the dynamic expression of Qa-2 in skin allografts by immunohistochemistry and on peripheral blood lymphocyte subsets by flow cytometry during the entire process of acute graft rejection (AGR) with a murine skin transplantation model to determine its relationship with the pathological changes of allografts and the influence of immunosuppressive therapy. In grafts without immunosuppressive treatment, Qa-2 did not exhibit obvious changes in syngeneic and allogeneic recipients. In contrast, with immunosuppressant-treated grafts, positive expression of Qa-2 was observed. It remained at high levels in the immunosuppressant-treated syngeneic group; however, it became weakly positive and even negative in infiltrating inflammatory cells as AGR advanced, but it remained strongly positive in other skin tissues throughout the AGR process. Qa-2 expression on CD4+ and CD8+ peripheral blood lymphocyte subsets remained stable at a normal level in the non–immunosuppressant-treated syngeneic group. Immunosuppressive treatment can also significantly upregulate Qa-2. In the allogeneic groups, decreased expression was observed when AGR was at histological grades 1 to 2 (well before gross rejection was observed). Qa-2 was upregulated again after the graft was rejected completely. The results suggest that the increase in Qa-2 may be attributed to the use of immunosuppressive treatments. Moreover, Qa-2 expression decreased significantly with AGR progression, suggesting that it may be a potential marker for predicting AGR, especially in the presence of immunosuppressive agents