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International Immunology, Vol. 13, No. 7, 887-896, July 2001
© 2001 Japanese Society for Immunology

Cytometric and functional analyses of NK and NKT cell deficiencies in NOD mice

Lynn D. Poulton, Mark J. Smyth1,, Christine G. Hawke, Pablo Silveira, Darren Shepherd, Olga V. Naidenko3,, Dale I. Godfrey2, and Alan G. Baxter Centenary Institute of Cancer Medicine and Cell Biology, Locked bag #6, Newtown, NSW 2042, Australia
1 Research Division, Peter MacCallum Cancer Institute, St Andrews Place, East Melbourne, Victoria 3002, Australia
2 Department of Pathology and Immunology, Monash University Medical School, Commercial Rd, Prahran, Victoria 3181, Australia
3 Division of Developmental Immunology, La Jolla Institute of Allergy and Immunology, San Diego, CA 92121, USA

Correspondence to: A. G. Baxter; Email: A.Baxter{at}Centenary.usyd.edu.au

Defects in NK and NKT cell activities have been implicated in the etiology of type 1 (autoimmune) diabetes in NOD mice on the basis of experiments performed using surrogate phenotypes for the identification of these lymphocyte subsets. Here, we have generated a congenic line of NOD mice (NOD.b-Nkrp1b) which express the allelic NK1.1 marker, enabling the direct study of NK and NKT cells in NOD mice. Major deficiencies in both populations were identified when NOD.b-Nkrp1b mice were compared with C57BL/6 and BALB.B6-Cmv1r mice by flow cytometry. The decrease in numbers of peripheral NK cells was associated with an increase in their numbers in the bone marrow, suggesting that a defect in NK cell export may be involved. In contrast, the most severe deficiency of NKT cells found was in the thymus, indicating that defects in thymic production were probably responsible. The deficiencies in NK cell activity in NOD mice could only partly be accounted for by the reduced numbers of NK cells, and fewer NKT cells from NOD mice produced IL-4 following stimulation, suggesting that NK and NKT cells from NOD mice shared functional deficiencies in addition to their numerical deficiencies. Despite the relative lack of IL-4 production by NOD NKT cells, adoptive transfer of {alpha}ßTCR+NK1.1+ syngeneic NKT cells into 3-week-old NOD recipients successfully prevented the onset of spontaneous diabetes. As both NK and NKT cells play roles in regulating immune responses, we postulate that the synergistic defects reported here contribute to the susceptibility of NOD mice to autoimmune disease.

Keywords: autoimmunity, cytokines, cytotoxicity, immunoregulation, type 1 diabetes

Transmitting editor: A. Kelso


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