[Human fetal pancreatic islet transplantation in insulin-dependent diabetics: possibilities of early detection of transplant destruction].
The factors determining the outcome of human fetal islet transplantation in patients with insulin-dependent diabetes mellitus (IDDM) remain unclarified. In this study we analysed the ratio between immunoregulatory lymphocyte subpopulations in order to search for a possible marker of the immune destruction of transplanted islets. Human fetal islets were isolated by collagenase digestion, cultured for 14 days at 37 degrees C, 5% CO2, and implanted under fascia of m. rectus abdominis in 7 IDDM patients (5 pancreata per patient). After transplantation we evaluated simultaneously the level of metabolic control through HbA1c values determined by chromatography, the capacity of insulin secretion through the C-peptide levels (determined by radioimmunoassay) before and 6 minutes after 1 mg glucagon i.v. stimulation, and the ratio between CD4+ and CD8+ lymphocytes determined by immunofluorescence using monoclonal antibodies. We found that metabolic control after transplantation was improved together with the decrease of the insulin daily dose, and the improvement was simultaneous to the increase of both basal and glucagon-stimulated C-peptide levels. Four months after transplantation we detected a remarkable decrease in the secretion capacity, accompanied by the necessity for an increase in daily insulin dose to maintain optimal metabolic control. However, the loss of islet function was preceded by the increase in CD4+/CD8+ ratio, thus reflecting the presumable accumulation of CD4+ inducer T-lymphocytes. When the islet secretion capacity was destroyed, we found a decrease in CD4+/CD8+ ratio, reflecting the recruitment of CD8+ effector cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Djordjević
P B
PB
Institute for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center, Belgrade, Yugoslavia.
Brkić
S
S
Lalić
N M
NM
Zamaklar
M
M
Dragasević
M
M
Radović
Z
Z
Popović
S
S
Banović
D
D
Dimitrijević
V
V
Savić
K
K
D000328:Adult; D016516:CD4-CD8 Ratio; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000196:embryology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male
D007328:Insulin
Tranplantacija ostrvaca humanog fetalnog pankreasa u insulin-zavisnih dijabeticara: mogućnost rane detekcije destrukcije transplantata.