Elevation of serum IgE level and peripheral eosinophil count during T lymphocyte-directed gene therapy for ADA deficiency: implication of Tc2-like cells after gene transduction procedure.
We have successfully carried out T-cell-directed gene therapy for a boy with severe combined immunodeficiency due to adenosine deaminase deficiency (ADA SCID) and unexpectedly found an elevation of serum IgE level and peripheral eosinophil count during the course. More than 90% of transduced cells cultured for 7-11 days before infusion into the patient were positive for CD8 and expressed Th2-type cytokine genes such as IL-4, IL-5 and IL-13. Furthermore, CD4(+) T-depleted PBMC (peripheral blood mononuclear cells) from the patient synthesized IgE in vitro by stimulation with IL-4. Collectively, these results suggested that Tc2-like cells in the transduced cells have distinct immunological functions to help IgE synthesis and activate eosinophils.
Kawamura
N
N
Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan. nobu-ka@med.hokudai.ac.jp
Ariga
T
T
Ohtsu
M
M
Yamada
M
M
Tame
A
A
Furuta
H
H
Kobayashi
I
I
Okano
M
M
Yanagihara
Y
Y
Sakiyama
Y
Y
D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics; D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D002675:Child, Preschool; D004804:Eosinophils; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007136:Immunoglobulins / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics; D007378:Interleukins / Q000235:genetics / Q000494:pharmacology; D007958:Leukocyte Count; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D015703:Antigens, CD; D007136:Immunoglobulins; D007378:Interleukins; D010835:Phytohemagglutinins; D007073:Immunoglobulin E; D007371:Interferon-gamma; D000243:Adenosine Deaminase