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Elevated Double Negative T Cells in Pediatric Autoimmunity

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Abstract

Purpose

Autoimmune diseases are thought to be caused by a loss of self-tolerance of the immune system. One candidate marker of immune dysregulation in autoimmune disease is the presence of increased double negative T cells (DNTs) in the periphery. DNTs are characteristically elevated in autoimmune lymphoproliferative syndrome, a systemic autoimmune disease caused by defective lymphocyte apoptosis due to Fas pathway defects. DNTs have also been found in the peripheral blood of adult patients with systemic lupus erythematosus (SLE), where they may be pathogenic. DNTs in children with autoimmune disease have not been investigated.

Methods

We evaluated DNTs in pediatric patients with SLE, mixed connective tissue disease (MCTD), juvenile idiopathic arthritis (JIA), or elevated antinuclear antibody (ANA) but no systemic disease. DNTs (CD3+CD56−TCRαβ+CD4−CD8−) from peripheral blood mononuclear cells were analyzed by flow cytometry from 54 pediatric patients including: 23 SLE, 15 JIA, 11 ANA and 5 MCTD compared to 28 healthy controls.

Results

Sixteen cases (29.6 %) had elevated DNTs (≥2.5 % of CD3+CD56−TCRαβ+ cells) compared to 1 (3.6 %) control. Medication usage including cytotoxic drugs and absolute lymphocyte count were not associated with DNT levels, and percentages of DNTs were stable over time. Analysis of multiple phenotypic and activation markers showed increased CD45RA expression on DNTs from patients with autoimmune disease compared to controls.

Conclusion

DNTs are elevated in a subset of pediatric patients with autoimmune disease and additional investigations are required to determine their precise role in autoimmunity.

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Acknowledgments

We would like to thank Drs. George Van Hare, David Balzer, and Katie Plax for their help in patient recruitment and sample acquisition. Funding for this project was provided by the Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (to M.A.C.) and by NIH training grant 5T32AR007279-34 (J.A.T.).

Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1 TR000448 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Division of Allergy/Immunology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA

    James A. Tarbox

  2. Department of Pediatrics, Division of Rheumatology, Washington University School of Medicine, 660 S. Euclid Ave, Box 8208, St. Louis, MO, 63110, USA

    Molly P. Keppel, Nermina Topcagic, Charles Mackin, Miriam Ben Abdallah, Kevin W. Baszis, Andrew J. White, Anthony R. French & Megan A. Cooper

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  1. James A. Tarbox
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Correspondence to Megan A. Cooper.

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Tarbox, J.A., Keppel, M.P., Topcagic, N. et al. Elevated Double Negative T Cells in Pediatric Autoimmunity. J Clin Immunol 34, 594–599 (2014). https://doi.org/10.1007/s10875-014-0038-z

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  • DOI: https://doi.org/10.1007/s10875-014-0038-z

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