Effects of Apoptosis in Human Activated Peripheral T-Lymphocytes by Immunosuppressive Drugs.

Immunosuppressive drugs are widely used for the prevention and treatment of graft rejection, graft-versus-host disease (GVHD) and autoimmune disorders. The major effect of immunosuppressive treatment is to prevent the activation-induced proliferation of T cells essential for the immune response. Nevertheless, the role of immunosuppressive drugs in regulating apoptosis in activated lymphocytes has not been clearly elucidated. For further investgation, we compared commonly used immunosuppressive drug mycophenolic acid (MPA) with cyclosporin A (CsA) for the influence of apoptosis in activated lymphocytes. Human Peripheral T-lymphocytes were activated by phytohemagglutinin (PHA). Cell morphology, DNA fragmentation, percentage of annexin V positive cells were measured by microscopic, electrophoretic and flow cytometric techniques respectively. Characteristic apoptotic morphology and DNA Ladder of activated T-lymphocytes were found in MPA treated group, but missing in CsA group. Treated with 0.1mmol/L ~10mmol/L MPA for 24h~48h, the Annexin V positive percentage of activated T-lymphocytes increased significantly(P<0.05), and with dose-dependant(r=0.752, P<0.001)and time-dependant(r=0.583, P=0.001)manner. Treated with 0.1mmol/L ~1mmol/L CsA for 24h~48h, the Annexin V positive percentage of activated T-lymphocytes decreased significantly(P<0.05). In conclusion, we found clinical relevant doses of MPA induced apoptosis in activated peripheral T-lymphocytes, whereas, CsA inhibited apoptosis. These results suggest that immunosuppressive drugs may exert immunomodulatory effects in transplantation in part by regulating apoptosis of activated lymphocytes. They can be classified according to their action on apoptosis-induction and inhibition and it would favour a rational combination therapy.