Temporary anti-CD25/CsA therapy induces a CD4+ T-cell-mediated tolerance in BB/OK rats.
Pancreatic islets obtained from the congenic LEW.1BB/OK rat strain (MHC identical, different in genetic background from BB/OK rats) were grated into diabetic BB/OK rats. The recipients were treated for 10 d with 1.0 mg/kg bw anti-IL2 receptor monoclonal antibody (ART-18) in combination with 1.5 mg/kg bw cyclosporin A, which resulted in indefinite graft survival in the majority of animals. The successfully treated recipients (normoglycaemia for > 120 days) relapsed immediately into hyperglycaemia after graft removal. A second donor-identical graft was accepted without any further immunotherapy, whereas MHC-different islet grafts (obtained from LEW.1A or DA rats) were rejected, demonstrating the induction of donor-specific tolerance. Splenocytes or thoracic duct lymphocytes (TDL) obtained from successfully treated recipients were transfused into naive diabetic BB/OK rats grafted with LEW.1BB/OK islets. Independent of the origin of the transfused cells, 64% of recipients maintained normoglycaemia for more than 120 days. To characterize the cell population(s) responsible for transfer of tolerance, B-lymphocytes were removed from the TDLs using the monoclonal antibody OX33 and magnetic beads. When OX33-depleted TDLs were transfused into naive diabetic BB/OK with a LEW.1BB/OK islet graft, all recipients maintained normoglycaemia. The OX33-depleted TDLs consisted only of CD4+ T-lymphocytes, which were either negative for CD45RC or coexpressed the CD45RC at low levels. We conclude that the cell-dependent tolerance transfer is mediated by a TH2-like suppressor cell.
Kuttler
B
B
Institute of Diabetes Gerhardt Katsch Karlsburg, University of Greifswald, Germany.
Kauert
C
C
Wanka
H
H
Diamantstein
T
T
Hahn
H J
HJ
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001402:B-Lymphocytes / Q000637:transplantation; D017252:CD3 Complex; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016572:Cyclosporine / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology; D007108:Immune Tolerance; D007167:Immunotherapy; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D007694:Killer Cells, Natural / Q000637:transplantation; D008212:Lymphocyte Depletion; D051381:Rats; D011913:Rats, Inbred BB / Q000276:immunology*; D011917:Rats, Inbred Lew; D015375:Receptors, Interleukin-2 / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013897:Thoracic Duct / Q000166:cytology
D000906:Antibodies; D017252:CD3 Complex; D015375:Receptors, Interleukin-2; D016572:Cyclosporine