Restoration of immune abnormalities in diabetic BB rats after pancreas transplantation. I. Macrochimerism of donor-graft-derived RT6+ T cells responsible for restoration of immune responsiveness and suppression of autoimmune reaction.
Diabetes-prone (DP) BB rats (RT1(u), RT6.1) spontaneously develop insulin-dependent diabetes mellitus (IDDM) and the disease manifestation resembles that in human IDDM. DP rats are immunodeficient with severe T lymphocytopenia due to the absence of T cells expressing the RT6 differential alloantigen, which have immunoregulatory functions. MHC- and non-MHC-compatible Wistar Furth (WF; RT1(u), RT6.2) pancreases were transplanted into DP rats. WF pancreas grafts were destroyed by IDDM recurrence (insulitis), but not by rejection, with a mean survival time of 65.3 +/- 21.7 days. To prevent the recurrence of IDDM in the grafts, monoclonal antibodies to intercellular adhesion molecule-1 and leukocyte function-associated antigen-1 were administered. WF pancreas grafts were indefinitely accepted (>108.0 +/- 26.8 days) in monoclonal antibody-treated DP recipients. The number of T cells was increased and cellular immune responses restored only in the DP rats that had accepted grafts. The increased number of T cells was due to the peripheral appearance of donor-type RT6.2+ T cells, which represented 34.3 +/- 7.0% of total splenic T cells. The cytotoxicity of splenic T cells to WF islet cells was suppressed in the presence of RT6+ T cells in vitro. These findings demonstrated that stable macrochimerism of donor-derived RT6+ T cells could restore the immune responses and prevent the recurrence of IDDM in the DP recipients.
Uchikoshi
F
F
First Department of Surgery, Biomedical Research Center, Osaka University Medical School, Osaka.
Ito
T
T
Kamiike
W
W
Nakao
H
H
Makino
S
S
Miyasaka
M
M
Nozawa
M
M
Matsuda
H
H
D036002:ADP Ribose Transferases; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000945:Antigens, Differentiation, T-Lymphocyte; D015551:Autoimmunity; D002678:Chimera; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D005434:Flow Cytometry; D058851:GPI-Linked Proteins; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D051379:Mice; D016035:Pancreas Transplantation / Q000276:immunology*; D051381:Rats; D011913:Rats, Inbred BB; D011920:Rats, Inbred WF; D013601:T-Lymphocytes / Q000276:immunology*; D016559:Tacrolimus / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D036002:ADP Ribose Transferases; C449301:ART1 protein, human; C449322:Art2a protein, mouse; C449339:Art2b protein, mouse; C090163:Art2b protein, rat; D016559:Tacrolimus