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PMID: 9529321 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

alpha/beta-T cell receptor (TCR)+CD4-CD8- (NKT) thymocytes prevent insulin-dependent diabetes mellitus in nonobese diabetic (NOD)/Lt mice by the influence of interleukin (IL)-4 and/or IL-10.

The Journal of experimental medicine ·Vol. 187 ·No. 7 ·1998-04-06 ·Pages 1047-56

Hammond KJ, Poulton LD, Palmisano LJ, Silveira PA, Godfrey DI, Baxter AG

Abstract

We have previously shown that nonobese diabetic (NOD) mice are selectively deficient in alpha/beta-T cell receptor (TCR)+CD4-CD8- NKT cells, a defect that may contribute to their susceptibility to the spontaneous development of insulin-dependent diabetes mellitus (IDDM). The role of NKT cells in protection from IDDM in NOD mice was studied by the infusion of thymocyte subsets into young female NOD mice. A single intravenous injection of 10(6) CD4-/lowCD8- or CD4-CD8- thymocytes from female (BALB/c x NOD)F1 donors protected intact NOD mice from the spontaneous onset of clinical IDDM. Insulitis was still present in some recipient mice, although the cell infiltrates were principally periductal and periislet, rather than the intraislet pattern characteristic of insulitis in unmanipulated NOD mice. Protection was not associated with the induction of "allogenic tolerance" or systemic autoimmunity. Accelerated IDDM occurs after injection of splenocytes from NOD donors into irradiated adult NOD recipients. When alpha/beta-TCR+ and alpha/beta-TCR- subsets of CD4-CD8- thymocytes were transferred with diabetogenic splenocytes and compared for their ability to prevent the development of IDDM in irradiated adult recipients, only the alpha/beta-TCR+ population was protective, confirming that NKT cells were responsible for this activity. The protective effect in the induced model of IDDM was neutralized by anti-IL-4 and anti-IL-10 monoclonal antibodies in vivo, indicating a role for at least one of these cytokines in NKT cell-mediated protection. These results have significant implications for the pathogenesis and potential prevention of IDDM in humans.

MeSH Terms
Animals CD4-Positive T-Lymphocytes/immunology,metabolism CD8-Positive T-Lymphocytes/immunology,metabolism Cells, Cultured Diabetes Mellitus, Type 1/immunology,physiopathology Disease Models, Animal Flow Cytometry Histocytochemistry Interleukin-10/physiology Interleukin-4/physiology Interleukins/physiology Islets of Langerhans/cytology,immunology Killer Cells, Natural/immunology Lymphocyte Subsets/immunology Mice Mice, Inbred NOD Receptors, Antigen, T-Cell/metabolism Spleen/immunology Thymus Gland/metabolism Transplantation, Isogeneic/immunology
Chemicals
Interleukins Receptors, Antigen, T-Cell Interleukin-10 Interleukin-4
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Hammond K J
Autoimmunity Research Group, Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales 2042, Australia.
Poulton L D
Palmisano L J
Silveira P A
Godfrey D I
Baxter A G
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.187.7.1047
Published
1998-04-06
Pages
1047-56
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2212199
Subset
IM
External Links
PubMed source DOI: 10.1084/jem.187.7.1047 PMC Full Text View journal details
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