Accumulation of autoreactive effector T cells and allo-specific regulatory T cells in the pancreas allograft of a type 1 diabetic recipient.
OBJECTIVE
Simultaneous kidney-pancreas transplantation is an established treatment for patients with type 1 diabetes and end-stage renal failure, even though restored beta cell function may become affected by recurrent islet autoimmunity or graft rejection. We characterised infiltrating lymphocytes isolated from a pancreatic graft with normal endocrine function in a kidney-pancreas recipient with type 1 diabetes.


METHODS
The pancreas graft was removed due to recurrent graft pancreatitis of unknown cause. Pancreas-infiltrating lymphocytes and peripheral blood mononuclear cells (PBMC) were isolated and characterised phenotypically and functionally.


RESULTS
Compared with PBMC, pancreas-infiltrating lymphocytes exhibited a distinct activation/memory phenotype and T cell receptor profile that were indicative of selective infiltration of the pancreas. Islet autoreactive CD8(+) T cells could be detected in the pancreas and were increased in frequency compared with PBMC. Additionally, an augmentation of CD8(+) CD28(-) regulatory T cells was observed in the pancreas; these induced expression of the inhibitory receptor immunoglobulin-like transcript-3 on antigen-presenting cells in a donor HLA class I-specific manner.


CONCLUSIONS
These data demonstrate the simultaneous presence of regulatory and effector T cells in the pancreas allograft of a recipient with type 1 diabetes. They also indicate that circulating islet autoreactive T cells may reflect immunological processes in pancreatic tissue, even though their frequency in the periphery may lead to underestimation of their presence in the pancreas. Additional specificities were also present in the pancreas that were undetectable in the circulation.
Velthuis
J H
JH
Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, P.O. Box 9600, 2300 RC, Leiden, the Netherlands.
Unger
W W
WW
van der Slik
A R
AR
Duinkerken
G
G
Engelse
M
M
Schaapherder
A F
AF
Ringers
J
J
van Kooten
C
C
de Koning
E J
EJ
Roep
B O
BO
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000601:surgery; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology; D010179:Pancreas / Q000276:immunology*; D016035:Pancreas Transplantation / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous
D015703:Antigens, CD; D011948:Receptors, Antigen, T-Cell; D012313:RNA