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

Ivan Gerling, Mark A. Atkinson, Edward H. Leiter

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 Coxsackievirus 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. Studies in progress suggest that it exposure to islet cell autoantigens mediates IDDM protection by retarding the activation of islet autoreactive effector cells. In summary, although the mechanisms underlying IDDM retardation by introduction of islet cell autoantigens into the thymic micro-environment are not well understood, the method provides a useful bioassay for establishing the specific pathogenic potential of ‘candidate’ islet autoantigens.

Original languageEnglish (US)
Pages (from-to)851-858
Number of pages8
JournalJournal of Autoimmunity
Volume7
Issue number6
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Inbred NOD Mouse
Autoantigens
Type 1 Diabetes Mellitus
Thymus Gland
Islets of Langerhans
Glutamate Decarboxylase
Enterovirus
Peptides
Injections
Leukocytes
Animal Disease Models
Adoptive Transfer
Exudates and Transudates
Sequence Homology
Bovine Serum Albumin
Intraperitoneal Injections
Biological Assay
Membrane Proteins

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

The thymus as a site for evaluating the potency of candidate β cell autoantigens in NOD mice. / Gerling, Ivan; Atkinson, Mark A.; Leiter, Edward H.

In: Journal of Autoimmunity, Vol. 7, No. 6, 01.01.1994, p. 851-858.

Research output: Contribution to journalArticle

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