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Isolation of self antigen-reactive cells from inflamed islets of nonobese diabetic mice using CD4high expression as a marker
Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, CA 94305, USA.
Division of Immunology and Rheumatology, R-S021, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305-5111,USA .
1999 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 163, no 10, 5708-5714 p.Article in journal (Refereed) Published
Abstract [en]

The low precursor frequency of Ag-reactive CD4+ T cells has been a barrier to the study of CD4+ T cell responses to conventional Ags as well as CD4+ T cell responses to autoantigens recognized during the course of an autoimmune disease. We have recently reported that all "conventional Ag" reactive CD4+ T cells are contained within the subpopulation expressing high levels of the CD4 molecule, termed CD4high. We have identified a CD4high population in the islets of Langerhans of prediabetic nonobese diabetic (NOD) mice that is extremely potent in transferring disease. As few as 500 CD4high islet-infiltrating CD4+ T cells transferred insulin-dependent diabetes mellitus to CD8 reconstituted NOD-SCID mice within 30 days of transfer. In contrast, CD4high T cells isolated from either NOD spleen or salivary glands did not transfer insulin-dependent diabetes mellitus into similar CD8-reconstituted NOD-SCID recipients. These data indicate that the precursor frequency of NOD islet-reactive, pathogenic CD4+ T cells is much higher in the prediabetic NOD pancreas than in these other organs. The islet-infiltrating CD4high T cells displayed selected memory markers, by cell surface analysis, and displayed a Th 1 phenotype by RNase protection assay, but had a marked decrease in IL-4 mRNA determined by quantitative real time PCR when compared with the less pathogenic CD4normal islet-infiltrating T cells. Use of the CD4high marker to select Ag activated T cells represents a tool to isolate and study pathogenic CD4+ T cells from autoimmune lesions in which the Ag has not been previously defined.

Place, publisher, year, edition, pages
The American Association of Immunologists , 1999. Vol. 163, no 10, 5708-5714 p.
Keyword [en]
insulin-dependent diabetes mellitus, nonobese diabetic, RNase protection assay, limiting dilution analysis, propidium iodide
National Category
Basic Medicine
Research subject
URN: urn:nbn:se:umu:diva-87516PubMedID: 10553102OAI: diva2:709621
The Wenner-Gren Foundation

This work was supported by National Institutes of Health Grants PO1 AI 39646 and RO1 DK39959, and Juvenile Diabetes Foundation Research Grant 1-1999 supported this work. K.L was supported by the Wenner-Gren Foundations (Stockholm, Sweden) and by the Blanceflour-Ludovisi, Born Bildt Foundation (Stockholm).

Available from: 2014-04-02 Created: 2014-04-02 Last updated: 2014-04-10Bibliographically approved

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