T-cell reactivity to 38 kD insulin-secretory-granule protein in patients with recent-onset type 1 diabetes.
Type 1 diabetes seems to be an autoimmune disease in which T cells have a substantial role. A possible target antigen was suggested by the proliferation of CD4 T cells from a newly diagnosed patient in response to a 38 kD polypeptide of the insulin-secretory-granule membrane. To see whether this reactivity is widespread at disease onset, we have generated T-cell lines in vitro from peripheral blood mononuclear cells of nineteen children of caucasoid origin with newly diagnosed type 1 diabetes and sixteen healthy controls matched for age and HLA antigens. The procedure involved two cycles of incubation with a rat beta-cell tumour subcellular fraction enriched in secretory granules and plasma membrane components, followed by a proliferation assay. Fourteen (74% [95% confidence interval 49-91%]) of the patients' cell lines showed a positive proliferative response on subsequent exposure to the islet-cell antigen preparation compared with only two (13% [2-38%]) of the controls (p = 3 x 10(-4); difference 61% [44-87%]). Two subjects who had high titres of islet-cell autoantibodies (ICA) without clinical diabetes produced responsive T-cell lines. Reactivity towards the 38 kD fraction of insulin-secretory-granule membranes was found only in patients (eight of ten responders tested; 95% CI 44-98%) and one ICA-positive non-diabetic subject. Detection of an ongoing autoimmune T-cell response might be useful diagnostically and could lead to prevention of diabetes through specific immunotherapy.
Department of Immunohaematology and Blood Bank, University Hospital Leiden, The Netherlands.
B O
BO
Roep
A A
AA
Kallan
W L
WL
Hazenbos
G J
GJ
Bruining
E M
EM
Bailyes
S D
SD
Arden
J C
JC
Hutton
R R
RR
de Vries
D000293:Adolescent; D001323:Autoantibodies / Q000032:analysis; D001324:Autoantigens / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects*; D002478:Cells, Cultured; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000494:pharmacology*
D001323:Autoantibodies; D001324:Autoantigens; D007328:Insulin; D008565:Membrane Proteins; C024211:islet cell antibody