A multiplicity of protein antigens in subcellular fractions of rat insulinoma tissue are able to stimulate T cells obtained from non-obese diabetic mice.
Type 1 (insulin-dependent) diabetes mellitus is a T-cell mediated autoimmune disease with a number of different proteins being implicated as target autoantigens. A 38 kDa protein residing in the insulin secretory granule of insulinoma tissue is recognized by T-cell clones from a newly-diagnosed Type 1 diabetic patient. We have investigated the capacity of normal rat pancreatic beta-cell extracts and various subcellular fractions of transplantable RIN tissue to induce proliferation of T cells from non-obese diabetic (NOD) mice and H-2 identical NON.NOD-H-2g7 control mice. Normal rat islet beta-cell protein fractions induced intense, dose-dependent proliferation of NOD splenic T cells, but only marginal proliferative responses of NON.NOD-H-2g7 splenic T cells. To further localize the target antigens, four different subcellular fractions from RIN tissue were used as a source of antigen; here in particular the cytosolic proteins showed dose-dependent activation capacity with splenic T cells in NOD animals. These activities were absent in control mice. There was no proliferation after incubation with microsome preparations from other rat endocrine tissues. Purified carboxypeptidase H did not have any stimulatory activity on NOD T cells. Fractionation of the RIN cytosolic proteins showed a large number of different fractions eliciting proliferative activity. These results demonstrate that NOD T cells respond to a large number of potential islet beta-cell target antigens and it will be necessary to utilize NOD T-cell clones to identify the number and nature of these antigens.
Bieg
S
S
Department of Internal Medicine, University Hospital Ulm, FRG.
Bailyes
E M
EM
Yassin
N
N
Amann
J
J
Herberg
L
L
McGregor
A M
AM
Scherbaum
W A
WA
Banga
J P
JP
D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000494:pharmacology; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology; D005260:Female; D007340:Insulinoma / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology*; D008285:Major Histocompatibility Complex; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000276:immunology*; D051381:Rats; D012016:Reference Values; D013154:Spleen / Q000276:immunology; D013347:Subcellular Fractions / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm