Effect of mizoribine on effector T cell-mediated immune responses in mice.
T cells play a principal role in cellular immunity and govern the regulatory mechanism in humoral immunity. Therefore, T cells play a key role as either effectors or regulators in the immune network. Mizoribine (MZR), an immunosuppressive agent, suppresses both humoral and cellular immunity by acting on both T cells and B cells. In this study, we examined the effect of MZR on various effector T cell-mediated immune responses in mice. MZR prolonged skin graft survival and suppressed a localized graft-versus-host reaction (GvHR) and sheep red blood cell (SRBC)-induced delayed-type hypersensitivity (DTH) reaction. In a collagen-induced arthritic mice model, MZR reduced the arthritic index and the swelling of the hind limbs. Furthermore, MZR suppressed both bone damage and histopathological changes in the hind limbs. Interestingly, MZR markedly suppressed the DTH reaction to type II collagen (CII) but had no effect on anti-CII antibody levels in this arthritic model. In these models, effector T cells such as cytotoxic T lymphocyte (CTL) and TDTH cell play an important part in the development of these reactions. It is suggested that MZR inhibited these reactions via the inhibition of the effector T cell-mediated immune response. Therefore, it is also suggested that the suppressive effect of MZR on clinical rejection and autoimmune disease is based on its suppression of the effector T cell-mediated immune response, that is cellular immunity, in addition to humoral immunity.
Kamada
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Inoue
N
N
Takaoka
Y
Y
Nakagami
K
K
Mori
H
H
Nagai
H
H
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology; D003094:Collagen; D004912:Erythrocytes / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology; D006614:Hindlimb / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012263:Ribonucleosides / Q000494:pharmacology*; D012756:Sheep / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D007166:Immunosuppressive Agents; D012263:Ribonucleosides; C010052:mizoribine; D003094:Collagen