CD4 T-cell regulation of cytotoxic T cells during the induction phase of liver-induced spontaneous tolerance in rats.
OBJECTIVE
To check for in vivo CD4 T-cell-mediated inhibition of the immune response in rats with spontaneously accepted liver transplants.


METHODS
Using the Lewis to Wistar Furth rat strain combination, we performed transient in vivo depletion of CD4 T-cells by anti-CD4 monoclonal antibodies (mAb) after liver transplantation. We used the CTL assay to detect primed T cells. We also retransplanted a grafted donor liver, parked for 3 days, into a secondary naive recipient rat.


RESULTS
When Lewis rat livers were transplanted into the recipient Wistar Furth rats, the grafts suffered an early immune attack, followed by spontaneous acceptance without immunosuppression. However, giving anti-CD4 mAb to the recipients at the time of grafting prolonged the acute rejection reaction. Furthermore, giving anti-CD4 therapy on postoperative days (PODs) 21 and 35, but not on PODs 56 and 100, induced transient liver damage in recipients overcoming acute rejection. No primed T cells were detected by the CTL assay in the recipient rats within 2 months after transplantation. Meanwhile, the retransplanted liver had no ability to elicit an immune attack.


CONCLUSIONS
CD4 T cells seemed to downregulate the effector function of T cells, but not T-cell proliferation in this model.
Ishii
Tatsuhiro
T
Department of Surgery II, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.
Yamaguchi
Junzo
J
Gu
Weili
W
Hashimoto
Toshiaki
T
Yamamoto
Takao
T
Kanematsu
Takashi
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000911:Antibodies, Monoclonal; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000502:physiology*; D015536:Down-Regulation; D007111:Immunity, Cellular; D016031:Liver Transplantation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D011920:Rats, Inbred WF; D013601:T-Lymphocytes / Q000276:immunology*; D023001:Transplantation Tolerance / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin