Faculty Research 1990 - 1999

Title

The thymus as a site for evaluating the potency of candidate beta cell autoantigens in NOD mice.

Document Type

Article

Publication Date

1994

Keywords

Animal, Comparative-Study, Diabetes-Mellitus-Insulin-Dependent: im, Evaluation-Studies, Female, Glutamate-Decarboxylase: im, Immunization-Passive, Islets-of-Langerhans: im, Mice, Mice-Inbred-NOD, Molecular-Sequence-Data, Proteins: im, SUPPORT-U-S-GOVT-P-H-S, Thymus-Gland: im

JAX Source

J Autoimmun 1994 Dec;7(6):851-8

Grant

DK45342/DK/NIDDK, DK27722/DK/NIDDK, DK36175/DK/NIDDK

Abstract

Intrathymic (i.t.) injection of islet cells or whole islets retards development of insulin dependent diabetes mellitus (IDDM) in spontaneous animal models of the disease. Protection of 4-week-old prediabetic NOD/Lt female mice from subsequent IDDM development was specific for the it route of administration since intraperitoneal injection of an equal number of syngeneic islets failed to retard IDDM. The protective effect of i.t. injection of islet cells was compared with the effect of i.t. injection of syngeneic peritoneal exudate cells, NIT-1 cells, bovine serum albumin (BSA), ABBOS peptide, a 52 kDa islet cell membrane protein, various synthetic peptides from human glutamic acid decarboxylase (GAD) and a Coxsackievirus B4-derived peptide with homology to GAD. Interestingly, only a GAD-derived peptide containing sequence homology to Coxsackie-virus B4, and the corresponding Coxsackievirus B4-derived peptide, delayed IDDM onset. To establish the immunological mechanism underlying the reduced IDDM incidence following i.t. injection of islet cells, adoptive transfer of splenic leukocytes into NOD-scid/scid mice was performed. Splenic leukocytes from i.t.-injected non-diabetic females transferred IDDM into NOD-scid/scid recipients, but more slowly than splenocytes from unmanipulated, diabetic (control) donors. Co-transfer of 1:1 mixtures of splenic leukocytes from it islet-injected (and diabetes-free) NOD/Lt females and from untreated NOD/Lt diabetic donors produced IDDM as rapidly as splenocytes from diabetic donors injected alone. Hence, any peripheral suppression generated in i.t.-protected females was not sufficiently strong to prevent IDDM transfer by committed T-effector cells from the diabetic donors.(ABSTRACT TRUNCATED AT 250 WORDS)

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