FK506--its influence on anti-class 1 MHC alloantibody responses to blood transfusions.
The influence of FK506 on in vivo alloantibody responses to major histocompatability class 1 antigens was investigated in inbred rat strains, and compared with the effect of cyclosporine. AO rats received transfusions of DA blood on days 0 and 7. From days 0 to 14 the rats also received, daily, either FK506 0.3 mg/kg suspended in saline or dissolved in olive oil, or CsA 10 mg/kg. The administration of FK506 suspended in saline at the time of blood transfusion completely abrogated the development of anti-MHC class 1 alloantibodies as detected by indirect hemagglutination (IHA)* and 51Cr release complement dependent cytotoxicity assays (CDC). Isotyping studies showed that FK506 suspended in saline suppressed IgM production and inhibited the switch to IgG production. Similar responses were seen in CsA-treated animals. In contrast, rats treated with FK506 dissolved in olive oil developed high titers of anti-class 1 alloantibodies. On days 49 and 56 the rats were challenged with further DA blood transfusions given without immunosuppression. In the groups given FK506 suspended in saline or CsA, cytotoxic antibodies did not develop; low titer antibodies were, however, detected by IHA in the animals that had previously received FK506 suspended in saline. The results indicate that FK506, in common with CsA, inhibits anti-class 1 MHC alloantibody production, and at the same time enables the development of tolerance. The vehicle in which FK506 is administered is, however, critical to its efficacy at the low doses used. These results may be of relevance to clinical transplantation as similar antibodies mediate hyperacute renal allograft rejection in man.
Department of Medicine and Therapeutics, University of Aberdeen, Scotland.
D J
DJ
Propper
J
J
Woo
A W
AW
Thomson
G R
GR
Catto
A M
AM
Macleod
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000917:Antibody Formation / Q000187:drug effects; D001803:Blood Transfusion; D003524:Cyclosporins / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007518:Isoantibodies / Q000096:biosynthesis*; D008285:Major Histocompatibility Complex; D051381:Rats; D011919:Rats, Inbred Strains; D016559:Tacrolimus
D000900:Anti-Bacterial Agents; D003524:Cyclosporins; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D016559:Tacrolimus