A comparative study of T-cell receptor V beta usage in non-obese diabetic (NOD) and I-E transgenic NOD mice.
The non-obese diabetic (NOD) mouse is a model for the study of insulin-dependent diabetes mellitus (IDDM). Recently transgenic NOD mice have been derived (NOD-E) that express the major histocompatibility complex (MHC) class II I-E molecule. NOD-E do not become diabetic and show negligible pancreatic insulitis. The possibility pertained that NOD-E mice are protected from disease by a process of T-cell deletion or anergy. This paper describes our attempts to discover whether this was so, by comparing NOD and NOD-E mouse T-cell receptor V beta usage. Splenocytes and lymph node cells were therefore tested for their ability to proliferate in response to monoclonal anti-V beta antibodies. We were unable to show any consistent differences between NOD and NOD-E responses to the panel of antibodies used. Previously proposed V beta were shown to be unlikely candidates for deletion or anergy. T cells present at low frequency (V beta 5+) in both NOD and NOD-E mice were shown to be as capable of expansion in response to antigenic stimulation as were more frequently expressed V beta. Our data therefore do not support deletion or anergy as mechanisms which could account for the observed disease protection in NOD-E mice.
Department of Pathology, University of Cambridge, U.K.
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NM
Parish
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Acha-Orbea
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E
Simpson
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SX
Qin
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T
Lund
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Cooke
D000818:Animals; D002455:Cell Division / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D017353:Gene Deletion; D006183:H-2 Antigens / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D006183:H-2 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D010047:Ovalbumin