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Originally published online as doi:10.1189/jlb.1106654 on December 6, 2006

Published online before print December 6, 2006
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(Journal of Leukocyte Biology. 2007;81:654-662.)
© 2007 by Society for Leukocyte Biology

Reduced CD4+ subset and Th1 bias of the human iNKT cells in Type 1 diabetes mellitus

Janos Kis*,{dagger}, Peter Engelmann*,{ddagger}, Klara Farkas*,§, Geoffrey Richman*, Shawn Eck*, James Lolley*, Heyam Jalahej*, Maciej Borowiec||, Sally C. Kent, Andras Treszl* and Tihamer Orban*,1

* Section on Immunology and Immunogenetics and
|| Genetics and Epidemiology, Joslin Diabetes Center, and
Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA;
{dagger} Department of Internal Medicine, Polyclinic of the Hospitaller Brothers of St. John, Budapest, Hungary;
{ddagger} Department of Immunology and Biotechnology, Faculty of Medicine, University of Pecs, Pecs, Hungary; and
§ III. Department of Medicine, Bajcsy-Zsilinszky Hospital, Budapest, Hungary

1 Correspondence: Section on Immunology and Immunogenetics, Joslin Diabetes Center, One Joslin Place, Boston, MA, 02215, USA. E-mail: tihamer.orban{at}joslin.harvard.edu

Invariant NKT (iNKT) cells are considered to be important in some autoimmune diseases including Type 1 diabetes mellitus (T1DM). So far, the published data are contradictory in regard to the role of iNKT cells in T1DM. We aimed to study iNKT cell frequency and the function of different iNKT cell subgroups in T1DM. We compared the results of four subject groups: healthy (H), long-term T2DM (ltT2DM; more than 1 year), newly diagnosed T1DM (ndT1DM; less than 3 months), and ltT1DM (more than 1 year) individuals. We measured the iNKT cell frequencies by costaining for the invariant TCR {alpha}-chain with 6B11-FITC and V{alpha}24-PE. After sorting the V{alpha}24+6B11+ cells, the generated iNKT clones were characterized. We tested CD4, CD8, and CD161 expression and IL-4 and IFN-{gamma} production on TCR stimulation. The CD4+ population among the iNKT cells was decreased significantly in ltT1DM versus ndT1DM, ltT2DM, or H individuals. The T1DM iNKT cell cytokine profile markedly shifted to the Th1 direction. There was no difference in the frequency of iNKT cells in PBMC among the different patient groups. The decrease in the CD4+ population among the iNKT cells and their Th1 shift indicates dysfunction of these potentially important regulatory cells in T1DM.

Key Words: autoimmunity • V{alpha}24+6B11+ cells • cytokines




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