The effectiveness of anti-Ia-immunotoxins in the suppression of MLR.
The potential use of a mouse anti-Ia monoclonal antibody conjugated with a plant toxin as an immunosuppressive agent for organ transplantation was examined by studying the mixed lymphocyte reaction (MLR). In initial observations in a murine system utilizing strains A/J and C57B1/6 (B6), it was shown that a rich-toxin-conjugated anti-I-Ek monoclonal antibody (13.4-immunotoxin) would kill Ia-bearing cells of strain A/J (I-Ek)--but not of strain B6, the cells of which lack I-E determinants. Studies reported here demonstrated that 13.4-immunotoxin effectively removed stimulatory cells from the I-E-bearing spleen cells but had no effect on spleen cells lacking I-E determinants or responder lymph node cells (I-E+ or I-E-) similarly treated (i.e., 1 microgram/10(6) cells). Taking advantage of the finding that such anti-I-E antibodies react with rat spleen cells bearing class II major histocompatibility complex molecules, we utilized these toxin-conjugated antibodies to inhibit MLR in rats. Assuming that the MLR is an in vitro representative of graft rejection, we suggest that such immunotoxins might be useful for pretreatment of organ allografts for transplantation across major histocompatibility barriers.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D003603:Cytotoxins / Q000627:therapeutic use; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007108:Immune Tolerance; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D012276:Ricin / Q000276:immunology; D013154:Spleen / Q000166:cytology
D000911:Antibodies, Monoclonal; D003603:Cytotoxins; D000949:Histocompatibility Antigens Class II; D012276:Ricin