Elevated double negative T cells in pediatric autoimmunity.
OBJECTIVE
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.


CONCLUSIONS
DNTs are elevated in a subset of pediatric patients with autoimmune disease and additional investigations are required to determine their precise role in autoimmunity.
Department of Internal Medicine, Division of Allergy/Immunology, Washington University School of Medicine, 660 S. Euclid Ave, St. Louis, MO, 63110, USA.
James A
JA
Tarbox
Molly P
MP
Keppel
Nermina
N
Topcagic
Charles
C
Mackin
Miriam
M
Ben Abdallah
Kevin W
KW
Baszis
Andrew J
AJ
White
Anthony R
AR
French
Megan A
MA
Cooper
D000293:Adolescent; D000974:Antibodies, Antinuclear / Q000097:blood; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015551:Autoimmunity / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D003603:Cytotoxins / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D006801:Humans; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008947:Mixed Connective Tissue Disease / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology; D013256:Steroids / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D055815:Young Adult
D000974:Antibodies, Antinuclear; D003603:Cytotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013256:Steroids; D017493:Leukocyte Common Antigens