Use of anti-L3T4 and anti-Ia treatments for prolongation of xenogeneic islet transplants.
The effects of T helper lymphocyte and Ia+ cell depletion were examined for their ability to independently and synergistically achieve prolongation of xenogeneic (rat-to-mouse) islet transplants. Recipient mice were depleted of T helper lymphocytes by short-term treatment with the anti-L3T4 monoclonal antibody GK1.5. Donor rat islets were treated prior to transplantation with a concentration of anti-Ia immunotoxin (13.4 x RT) that selectively depleted Ia+ cells within the islets while leaving functional insulin-secreting beta-cells unaffected. Anti-L3T4 treatment alone allowed transplants to be prolonged compared with untreated controls; however, all such treated mice rejected their xenogeneic transplant within 22 days. Although 13.4 x RT treatment of donor islets alone did not prolong engraftment, when donor rat islets were pretreated with the anti-Ia immunotoxin and grafted into L3T4-depleted mice, normoglycemia was maintained for greater than 50 days in 56% of transplants. These results suggest that neither L3T4 depletion nor anti-Ia immunotoxin treatment alone is enough to achieve indefinite survival of xenogeneic islets. However, decreasing the immunogenicity of the transplanted islets by anti-Ia immunotoxin treatment prior to transplantation into anti-L3T4 treated mice can allow greatly prolonged xenogeneic graft survival.
Kaufman
D S
DS
Department of Medicine, Stanford University Medical Center, California 94305.
Kong
C S
CS
Shizuru
J A
JA
Gregory
A K
AK
Fathman
C G
CG
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D000922:Immunotoxins; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D051381:Rats; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000949:Histocompatibility Antigens Class II; D000922:Immunotoxins