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Arndt, B.* ; Witkowski, L.* ; Ellwart, J.W. ; Seissler, J.

CD8+ CD122+ PD-1- effector cells promote the development of diabetes in NOD mice.

J. Leukoc. Biol. 97, 111-120 (2015)
Publ. Version/Full Text Research data DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
It is well established that CD4 and CD8 T cells are required for the initiation of autoimmune diabetes in NOD mice. However, different subsets of CD4 or CD8 cells may play different roles in the initiation of insulitis. In this study, we evaluated the role of the previously described CD8(+) CD122(+) in this process. We found that prediabetic NOD mice have an almost 50% reduction of CD8(+) CD122(+) T cells in their secondary lymphoid organs compared with BL/6 or Balb/c mouse strains. This reduction is explained by the lack of the regulatory CD8(+) CD122(+) PD-1(+) cell population in the NOD mice, as we found that all CD8(+) CD122(+) T cells from prediabetic NOD mice lack PD-1 expression and regulatory function. Depletion of CD8(+) CD122(+) PD-1(-) cells through injection of anti-CD122 mAb in prediabetic female NOD mice reduced the infiltration of mononuclear cells into the Langerhans islets and delayed the onset and decreased the incidence of overt diabetes. In addition, we found that transfer of highly purified and activated CD8(+) CD122(+) PD-1(-) cells, together with diabetogenic splenocytes from NOD donors to NOD SCID recipients, accelerates the diabetes development in these mice. Together, these results demonstrate that CD8(+) CD122(+) PD-1(-) T cells from NOD mice are effector cells that are involved in the pathogenesis of autoimmune diabetes.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords T Cells ; Autoimmunity ; Inflammation ; Insulitis; Regulatory T-cells; Chemokine Receptor Cxcr3; Ifn-gamma Production; In-vivo; Cutting Edge; Mouse; Model; Proliferation; Infiltration; Stimulation
ISSN (print) / ISBN 0741-5400
e-ISSN 1938-3673
Journal Journal of Leukocyte Biology
Quellenangaben Volume: 97, Issue: 1, Pages: 111-120 Article Number: , Supplement: ,
Publisher FASEB
Publishing Place Bethesda
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Molecular Immunology (IMI)
Institute of Experimental Genetics (IEG)
CCG Nutrigenomics and Type 2 Diabetes (KKG-KDN)