THE IMMUNOMODULATORY EFFECT OF CYCLOPHOSPHAMIDE ON REGULATION OF T-CELL SUBSETS AND ANTIGEN PRESENTING CELLS

摘要

The effect of cyclophosphamide (CYP) on the function of CD4 (Th1 and Th2) and CD8 T-lymphocytes and antigen presenting cells (APC) was studied. Experiments were performed in a rat allogeneic model using both in vivo and in vitro techniques. The results show that high doses of CYP inhibited all T-cell functions. By contrast, low doses of CYP (less than 25mg/kg) accelerated kidney allogarft rejection and affected CD4 T-helper rather than CD8 T-cells. At lower doses, CYP inhibited the activation of T-suppressor cell function but the activation of cytotoxicity. Low doses of CYP caused no significant effect on the stimulatory capacity of APC in MLR proliferation and suppressor assays. Lymph node cells from pre-treated animals produce abundant IL-2. In conclusion, CYP at lower doses preferentially inactivates Th2-cell dependent pathways and inducing Th1 type response. Therefore, CYP may selectively manipulate the cellular immune response. This finding could be improved new strategies for allergy treatment and development of cancer vaccine technologies. This report concerns the immunopharmacology aspects of CYP on the activation of Tc and Ts cells, which may be directed by different population ofTh1 and Th2 cells.