Prevention of diabetes in BB/Wor rats by injection of peritoneal exudate cells cultured in the presence of transforming growth factor beta (TGF-beta) and islet cells.
Studies of ocular immunity showed that incubation of peritoneal exudate cells with antigen in the presence of aqueous humor containing TGF-beta, conferred upon them the ability to systemically inhibit antigen-specific cellular immunity when injected into naive recipients. Since cell mediated immunity has been implicated in the destruction of the islets of Langerhans in diabetes, it was theorized that injection of naive diabetes prone BB/W or rats with peritoneal exudate cells pre-cultured in the presence of islet antigen and TGF-beta might similarly inhibit their anti-islet immune reactions and prevent their development of diabetes. 34.2% (13 of 38) of experimental recipient diabetes prone rats developed diabetes while 78.4% (29 of 37; p < 0.0005 compared to experimentals), 72.2% (13 of 18; p < 0.03 compared to experimentals), 68.8% (11 of 16; p < 0.09 compared to experimentals), and 77.7% (7 of 9; p < 0.08 compared to experimentals) of controls receiving peritoneal exudate cells pre-cultured alone, with TGF-beta, with TGF-beta and pheochromocytoma (PC12) cells, or with islets + TGF-beta + anti-TGF-beta antibody, respectively, became diabetic. Experimental treatment did not markedly alter recipient spleen cell subsets, and spleen cells from protected rats did not confer disease protection when transferred into naive recipients. These data demonstrate that the above approach is efficacious and represents a unique strategy for preventing the development of autoimmune type I diabetes in an animal model.
Koevary
S B
SB
Ocular Research and Biotechnology Center, New England College of Optometry, Boston, USA.
D000818:Animals; D001082:Aqueous Humor / Q000276:immunology; D002450:Cell Communication; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005122:Exudates and Transudates / Q000166:cytology*; D005434:Flow Cytometry; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D017710:Lymphocyte Transfusion; D008214:Lymphocytes / Q000276:immunology; D051381:Rats; D011913:Rats, Inbred BB; D013154:Spleen / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D016212:Transforming Growth Factor beta