T-cell receptor Vβ skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS.
Immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A, is effective in refractory cytopenia of childhood (RCC), suggesting that, similar to low-grade myelodysplastic syndromes in adult patients, T lymphocytes are involved in suppressing hematopoiesis in a subset of RCC patients. However, the potential role of a T-cell-mediated pathophysiology in RCC remains poorly explored. In a cohort of 92 RCC patients, we prospectively assessed the frequency of T-cell receptor (TCR) β-chain variable (Vβ) domain skewing in bone marrow and peripheral blood by heteroduplex PCR, and analyzed T-cell subsets in peripheral blood by flow cytometry. TCRVβ skewing was present in 40% of RCC patients. TCRVβ skewing did not correlate with bone marrow cellularity, karyotype, transfusion history, HLA-DR15 or the presence of a PNH clone. In 28 patients treated with IST, TCRVβ skewing was not clearly related with treatment response. However, TCRVβ skewing did correlate with a disturbed CD4(+)/CD8(+) T-cell ratio, a reduction in naive CD8(+) T cells, an expansion of effector CD8(+) T cells and an increase in activated CD8(+) T cells (defined as HLA-DR(+), CD57(+) or CD56(+)). These data suggest that T lymphocytes contribute to RCC pathogenesis in a proportion of patients, and provide a rationale for treatment with IST in selected patients with RCC.
1] Department of Pediatric Oncology/Hematology, Sophia Children's Hospital-Erasmus University Medical Center, Rotterdam, The Netherlands [2] Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands.
A M
AM
Aalbers
Department of Pediatric Oncology/Hematology, Sophia Children's Hospital-Erasmus University Medical Center, Rotterdam, The Netherlands.
M M
MM
van den Heuvel-Eibrink
Department of Pathology, Clinical Centre South West, Böblingen Clinics, Böblingen, Germany.
I
I
Baumann
Department of Clinical Genetics, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands.
H B
HB
Beverloo
1] Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands [2] Department of Pediatric Infectious Disease and Immunology, Sophia Children's Hospital-Erasmus University Medical Center, Rotterdam, The Netherlands.
G J
GJ
Driessen
Department of Pediatrics, St Anna Children's Hospital and Children's Cancer Research Institute, Medical University of Vienna, Vienna, Austria.
M
M
Dworzak
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
A
A
Fischer
Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.
G
G
Göhring
Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark.
H
H
Hasle
Department of Pediatric Hematology-Oncology, IRCCS Ospedale Bambino Gesù, Rome, University of Pavia, Pavia, Italy.
F
F
Locatelli
Department of Pediatric Hematology/Oncology, Ghent University Hospital, Ghent, Belgium.
B
B
De Moerloose
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
P
P
Noellke
Department of Hematology, University Children's Hospital, Zurich, Switzerland.
M
M
Schmugge
Department of Pediatric Hematology/Oncology, Charles University and University Hospital Motol, Prague, Czech Republic.
J
J
Stary
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
A
A
Yoshimi
Pediatric Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
M
M
Zecca
Department of Pediatric Oncology/Hematology, Sophia Children's Hospital-Erasmus University Medical Center, Rotterdam, The Netherlands.
C M
CM
Zwaan
Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands.
J J M
JJ
van Dongen
Department of Pediatric Oncology/Hematology, Sophia Children's Hospital-Erasmus University Medical Center, Rotterdam, The Netherlands.
R
R
Pieters
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
C M
CM
Niemeyer
Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands.
V H J
VH
van der Velden
Department of Immunology, Erasmus MC, Erasmus University Medical Center, Rotterdam, The Netherlands.
A W
AW
Langerak
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D008297:Male; D009190:Myelodysplastic Syndromes / Q000276:immunology* / Q000473:pathology; D010198:Pancytopenia / Q000276:immunology; D011446:Prospective Studies; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000737:chemistry*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta