Elevated Double Negative T Cells in Pediatric Autoimmunity

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.

Abnormal hematopoiesis and autoimmunity in human subjects with germline IKZF1 mutations

“…9 which were found in some patients with autoimmune diseases or primary immunodeficiencies mostly associated with autoimmunity (see Table E4 and Fig E6, A, in this article's Online Repository at www.jacionline.org). 21,22 Lack of gd T cells and a lower threshold of T-cell proliferation were observed, which were also described in mice (see Fig E6, B). 1,6,23 T cells from patient B.1, who had a history of Pneumocystis jirovecii pneumonia, exhibited a predominance of naive phenotype and a poor response to anti-CD3/CD28 antibody, which were different features from those of the other patients (see Table E4 and Fig E6, B).…”

Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial

“…11 Small numbers of DNTs circulate in healthy pediatric controls due to a reactive phenomenon and in conditions such as SLE. 8,11,12 Therefore, abnormally elevated numbers must exceed 1.5% of total lymphocytes or 2.6% of CD31 lymphocytes. 11 The percentage of DNTs was monitored in the majority of ALPS patients (N 5 9) before and after sirolimus.…”

Lymphocytic oesophagitis, eosinophilic oesophagitis and compound lymphocytic–eosinophilic oesophagitis I: histological and immunohistochemical findings

“…These experimental findings confirmed that lymphocytes are closely associated in the pathogenesis of EoE. In humans, Tarbox et al 38 found that mature T cells expressing CD3/TCR α/β receptor, lacking CD4/CD8 (known as double negative T cells), were elevated in paediatric patients with autoimmune disease. In patients with EoE, Jyonouchi et al 39 found that sphingolipids contained in milk may drive the development of EoE by promoting an invariant NK T cell-mediated Th2 cytokine response.…”