Reactivity to human islets and fetal pig proislets by peripheral blood mononuclear cells from subjects with preclinical and clinical insulin-dependent diabetes.
A simple, direct assay for T-lymphocyte reactivity to islet antigen(s) in human insulin-dependent diabetes mellitus (IDDM) should facilitate preclinical diagnosis and the evaluation of intervention therapy to avert autoimmune-mediated beta-cell destruction. In subjects with preclinical or clinical IDDM, we measured the reactivity of peripheral blood mononuclear cells (PBMCs) incubated over 6 days with either adult human islets or fetal pig proislets, or other fetal pig tissues, and with human insulin. With islets, the stimulation index (SI) of [3H]thymidine uptake by PBMCs exceeded the mean + 2SD of control subjects in 6 of 6 preclinical subjects (SI 8.7 +/- 3.7), 7 of 11 clinical subjects (SI 5.2 +/- 3.4), and 1 of 12 control subjects (SI 2.7 +/- 1.7); with insulin, the responses were less in frequency and magnitude, being 4 of 6 (2.7 +/- 1.6), 3 of 11 (2.2 +/- 1.1), and 0 of 12 (1.20 +/- 0.55), respectively. The mean responses to islets of PBMCs from preclinical and clinical subjects differed significantly from control subjects (P less than 0.02 by 2-tailed Kruskal-Wallis test). Secretion of granulocyte macrophage colony-stimulating factor by PBMCs over 6 days was assayed in the preclinical group and generally paralleled the uptake of [3H]thymidine. PBMC reactivity to islets appeared to be at least as sensitive a marker of preclinical IDDM as autoantibodies to a 64,000-Mr protein, presumably the enzyme glutamic acid decarboxylase, in fetal pig proislets. In conclusion, islet-reactive T lymphocytes in subjects with preclinical and clinical IDDM can be identified in bulk culture of PBMCs.(ABSTRACT TRUNCATED AT 250 WORDS)
Harrison
L C
LC
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Parkville, Victoria, Australia.
De Aizpurua
H
H
Loudovaris
T
T
Campbell
I L
IL
Cebon
J S
JS
Tait
B D
BD
Colman
P G
PG
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology; D002648:Child; D004261:DNA Replication; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005333:Fetus; D005968:Glutamate Decarboxylase / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000196:embryology / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D011236:Prediabetic State / Q000276:immunology*; D012016:Reference Values; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism
D001323:Autoantibodies; D006684:HLA-DR Antigens; D007328:Insulin; C024211:islet cell antibody; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D005968:Glutamate Decarboxylase; D013936:Thymidine