Effect of FK506 treatment on allocytolytic T lymphocyte induction in vivo: differential effects of FK506 on L3T4+ and Ly2+ T cells.
Although FK506 has been widely investigated as a potent suppressor of organ allograft rejection in animals, little is known about the effect of FK506 on T cell responses to allografts in vivo. In the present study, we have studied the effect of FK506 on the induction of allocytolytic T lymphocyte using mice primed with alloantigens and treated with FK506. FK506 suppressed the CTL induction of spleen cells and peritoneal exudate cells (PEC) in a dose-dependent manner. Time-course kinetic studies indicated that the CTL activity was markedly dependent on the time of administration of FK506 to the mice. Lymphocytes from these FK506-treated animals were found to be reactivated upon exposure to the same alloantigens in a secondary mixed lymphocyte culture (MLC). Furthermore, FK506 was shown to have a differential effect on the activation of helper (L3T4+) and cytotoxic (Ly2+) T cell subpopulations. L3T4+ T cells from the mice primed with alloantigens and treated with FK506 had normal helper activity in the generation of CTL in MLC, whereas Ly2+ T cells from these mice were profoundly suppressed CTL activity upon reexposure to the same alloantigens in a secondary MLC. Exogenous IL-2 or L3T4+ T cells could overcome the immunosuppressive effect of FK506 on the CTL induction of Ly2+ T cells in a secondary MLC. Finally, we have demonstrated that this FK506 effect appeared to be antigen nonspecific since Ly2+ T cells from alloprimed FK506-treated mice failed to induce CTL against the third-party alloantigens as well as the same alloantigens in a secondary MLC.
First Department of Internal Medicine, School of Medicine, Toyama Medical and Pharmaceutical University, Japan.
M
M
Maruyama
H
H
Suzuki
N
N
Yamashita
S
S
Yano
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000950:Antigens, Ly / Q000032:analysis; D001202:Ascitic Fluid / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D007111:Immunity, Cellular / Q000187:drug effects*; D007156:Immunologic Memory / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D007519:Isoantigens / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D016559:Tacrolimus; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000950:Antigens, Ly; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007519:Isoantigens; D016559:Tacrolimus