19
Dr J0rn Nerup, Dr Ole Ortved Andersen, Dr Gunnar Bendixen, Dr J0rn Egeberg, Dr Rolf Gunnarsson, Dr Claes Hellerstrom, Dr Hans Kromann and Dr Jacob E Poulsen (Medical Department F, Kobenhavns Amts Sygehus, Gentofte, Medical Department E, Frederiksberg Hospital, Medical Department TA, Rigshospitalet, Department ofAnatomy, University of Copenhagen. Department of Histology, University of Uppsala and Steno Memorial Hospital, Copenhagen, Denmark)
Section of Endocrinology
259
(2) a discrete lymphocytic infiltration of the islets at eight to nine days, accompanied by (3) severe degeneration and degranulation of the B and A cells; this lesion often proceeds to a cytolytic necrosis of the islets, and leads to (4) a significant but transient reduction of glucose tolerance two weeks after immunization.
After three to four weeks islet structure and function has recovered completely (Nerup, Ortved Andersen, Bendixen, Egeberg, Poulsen, Vilien & Westrup 1973, Nerup et al. 1974). Autoimmune Aspects This animal model of juvenile diabetes mellitus may serve as a useful tool for future studies of the The pathology of the endocrine pancreas in pathogenesis of spontaneous human juvenile early juvenile diabetes mellitus has two major diabetes mellitus. characteristics: (1) The functioning B cell mass is markedly reduced, due partly to a decrease in the REFERENCES W (1965) Diabetes 14, 619 number of islets, partly to a reduction in size of Gepts Irvine W J, Clarke B F, Scarth L, Cullen D R & Duncan L P J the remaining islets. (2) Lymphocytic infiltration (1970) Lancet ii, 163 Nerup J & Binder C in and around the islets (Gepts 1965). (1973) Acta endocrinologica 72, 279
Juvenile diabetes mellitus is often - clinically and serologically - associated with autoimmune disease of the thyroid gland, the gastric mucosa and the adrenal cortex (Irvine et al. 1970, Nerup & Binder 1973). Attempts to demonstrate organspecific antibodies to the endocrine pancreas have, so far, been unsuccessful. However, the structural and functional islet damage in juvenile diabetes mellitus could be the ultimate result of an immunological reaction between antigenic determinants of the endocrine pancreas and specifically reactive immunologically competent cells. In other words, cell-mediated immunity may play an important pathogenetic role in juvenile diabetes mellitus.
Organ-specific, antipancreatic cell-mediated immunity has in fact been demonstrated by means of the leukocyte migration test in about one third of the patients. It is predominantly found in patients with juvenile diabetes of short duration, irrespective of previous treatment with insulin. The precise biochemical nature of the antigen in question is unknown, but it is organ-specific, widely species-non-specific and different from insulin (Nerup, Ortved Andersen, Bendixen, Egeberg & Poulsen 1971, 1973). A condition in some respects similar to juvenile diabetes mellitus can be produced in experimental animals. Rats and mice immunized with single intracutaneous injections of heterologous or homologous endocrine pancreas in complete Freunds' adjuvant develop: (1) organ-specific, antipancreatic cell-mediated immunity, demonstrable in vitro by means of spleen cell migration inhibition, seven to eight days after immunization;
Nerup J, Ortved Andersen 0, Bendixen G, Egeberg J, Gunnarsson R, Kromann H & Poulsen J E (1974) Proceedings of the Royal Society of Medicine 67, 506-513 Nerup J, Ortved Andersen 0, Bendixen G, Egeberg J & Poulsen J E (1971) Diabetes 20, 424 (1973) Acta allergologica 28, 223 Nerup J, Ortved Andersen 0, Bendixen G, Egeberg J, Poulsen J E Vilien M & Westrup M (1973) Acta allergologica 28,231
The following papers were also read:
Autoimmunity in Experimental Animal Models: Experimentally Induced Orchitis Dr L E Glynn (MRC Rheumatism Research Unit, Canadian Red Cross Memorial Hospital, Taplow, Maidenhead, Berkshire) Spontaneous Thyroiditis in the Obese Strain (OS) of Chickens Dr G Wick (University of Vienna)
Thyroiditis in Thymectomized Irradiated Rats Dr W J Penhale, Dr A Farmer and Dr W J Irvine (Immunology Laboratories, 2 Forrest Road, Edinburgh) (see Journal ofEndocrinology, -1974,62 IP (abstract)
Dr J0rn Nerup, Dr Ole Ortved Andersen, Dr Gunnar Bendixen, Dr J0rn Egeberg, Dr Rolf Gunnarsson, Dr Claes Hellerstrom, Dr Hans Kromann and Dr Jacob E Poulsen (Medical Department F, Kobenhavns Amts Sygehus, Gentofte, Medical Department E, Frederiksberg Hospital, Medical Department TA, Rigshospitalet, Department ofAnatomy, University of Copenhagen. Department of Histology, University of Uppsala and Steno Memorial Hospital, Copenhagen, Denmark)
Section of Endocrinology
259
(2) a discrete lymphocytic infiltration of the islets at eight to nine days, accompanied by (3) severe degeneration and degranulation of the B and A cells; this lesion often proceeds to a cytolytic necrosis of the islets, and leads to (4) a significant but transient reduction of glucose tolerance two weeks after immunization.
After three to four weeks islet structure and function has recovered completely (Nerup, Ortved Andersen, Bendixen, Egeberg, Poulsen, Vilien & Westrup 1973, Nerup et al. 1974). Autoimmune Aspects This animal model of juvenile diabetes mellitus may serve as a useful tool for future studies of the The pathology of the endocrine pancreas in pathogenesis of spontaneous human juvenile early juvenile diabetes mellitus has two major diabetes mellitus. characteristics: (1) The functioning B cell mass is markedly reduced, due partly to a decrease in the REFERENCES W (1965) Diabetes 14, 619 number of islets, partly to a reduction in size of Gepts Irvine W J, Clarke B F, Scarth L, Cullen D R & Duncan L P J the remaining islets. (2) Lymphocytic infiltration (1970) Lancet ii, 163 Nerup J & Binder C in and around the islets (Gepts 1965). (1973) Acta endocrinologica 72, 279
Juvenile diabetes mellitus is often - clinically and serologically - associated with autoimmune disease of the thyroid gland, the gastric mucosa and the adrenal cortex (Irvine et al. 1970, Nerup & Binder 1973). Attempts to demonstrate organspecific antibodies to the endocrine pancreas have, so far, been unsuccessful. However, the structural and functional islet damage in juvenile diabetes mellitus could be the ultimate result of an immunological reaction between antigenic determinants of the endocrine pancreas and specifically reactive immunologically competent cells. In other words, cell-mediated immunity may play an important pathogenetic role in juvenile diabetes mellitus.
Organ-specific, antipancreatic cell-mediated immunity has in fact been demonstrated by means of the leukocyte migration test in about one third of the patients. It is predominantly found in patients with juvenile diabetes of short duration, irrespective of previous treatment with insulin. The precise biochemical nature of the antigen in question is unknown, but it is organ-specific, widely species-non-specific and different from insulin (Nerup, Ortved Andersen, Bendixen, Egeberg & Poulsen 1971, 1973). A condition in some respects similar to juvenile diabetes mellitus can be produced in experimental animals. Rats and mice immunized with single intracutaneous injections of heterologous or homologous endocrine pancreas in complete Freunds' adjuvant develop: (1) organ-specific, antipancreatic cell-mediated immunity, demonstrable in vitro by means of spleen cell migration inhibition, seven to eight days after immunization;
Nerup J, Ortved Andersen 0, Bendixen G, Egeberg J, Gunnarsson R, Kromann H & Poulsen J E (1974) Proceedings of the Royal Society of Medicine 67, 506-513 Nerup J, Ortved Andersen 0, Bendixen G, Egeberg J & Poulsen J E (1971) Diabetes 20, 424 (1973) Acta allergologica 28, 223 Nerup J, Ortved Andersen 0, Bendixen G, Egeberg J, Poulsen J E Vilien M & Westrup M (1973) Acta allergologica 28,231
The following papers were also read:
Autoimmunity in Experimental Animal Models: Experimentally Induced Orchitis Dr L E Glynn (MRC Rheumatism Research Unit, Canadian Red Cross Memorial Hospital, Taplow, Maidenhead, Berkshire) Spontaneous Thyroiditis in the Obese Strain (OS) of Chickens Dr G Wick (University of Vienna)
Thyroiditis in Thymectomized Irradiated Rats Dr W J Penhale, Dr A Farmer and Dr W J Irvine (Immunology Laboratories, 2 Forrest Road, Edinburgh) (see Journal ofEndocrinology, -1974,62 IP (abstract)
