A possible site of in vivo action of cyclosporin A for transplantation immunity: comparative study with cyclophosphamide.
The immunosuppressive mechanisms of cyclosporin A (CsA) and cyclophosphamide (CPM) in vivo were studied by measuring the transplantation immunity for second set rejection of an allogeneic ascites tumor. The transplantation immunity in our assay system was mediated primarily by allospecific cytotoxic T lymphocytes (CTL). Our results showed that both CsA and CPM did not affect the process of inducing the immunity, but they inhibited the effector phase of that transplant immunity. The experiments using 51Cr-release assay in vitro on peritoneal exudate cells as effector cells showed that the effector phase of the transplantation immunity in vivo involved the maturation from immunological memory CTL-precursor cells to effector CTL with clonal expansion. Further, adoptive cell transfer experiments showed that CsA did not eliminate the immunological memory CTL nor induce the suppressor cells in donor mice. All the data suggested that the maturation of memory CTL precursor cells to effector CTL was inhibited by CsA which would block lymphokine production even in vivo, whereas CPM eliminated the CPM-sensitive memory CTL precursor cells. The findings that CsA and CPM act on the different sites of CTL maturation support the possibility of effectiveness of the combination therapy of the two agents for controlling the transplantation immunity.
Hasegawa
Y
Y
Department of Immunology, Nagoya University School of Medicine, Japan.
Isobe
K
K
Nagase
F
F
Shimokata
K
K
Nakashima
I
I
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D006084:Graft Rejection / Q000187:drug effects; D007156:Immunologic Memory / Q000187:drug effects; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014181:Transplantation Immunology / Q000187:drug effects*
D016572:Cyclosporine; D003520:Cyclophosphamide