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

N Kawamura; T Ariga; M Ohtsu; M Yamada; A Tame; H Furuta; I Kobayashi; M Okano; Y Yanagihara; Y Sakiyama

doi:10.1016/s0165-2478(98)00083-2

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

Immunol Lett. 1998 Nov;64(1):49-53. doi: 10.1016/s0165-2478(98)00083-2.

Authors

N Kawamura¹, T Ariga, M Ohtsu, M Yamada, A Tame, H Furuta, I Kobayashi, M Okano, Y Yanagihara, Y Sakiyama

Affiliation

¹ Department of Pediatrics, Hokkaido University School of Medicine, Sapporo, Japan. [email protected]

PMID: 9865602
DOI: 10.1016/s0165-2478(98)00083-2

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Deaminase / deficiency*
Adenosine Deaminase / genetics
Antigens, CD / immunology
B-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / immunology
Cells, Cultured
Child, Preschool
Eosinophils*
Gene Transfer Techniques
Genetic Therapy*
Humans
Immunoglobulin E / blood*
Immunoglobulins / blood
Interferon-gamma / genetics
Interleukins / genetics
Interleukins / pharmacology
Leukocyte Count
Lymphocyte Activation / drug effects
Male
Phytohemagglutinins / pharmacology
Severe Combined Immunodeficiency / immunology*
Severe Combined Immunodeficiency / metabolism
Severe Combined Immunodeficiency / therapy
T-Lymphocytes / drug effects
T-Lymphocytes / immunology*
Th2 Cells / immunology

Substances

Antigens, CD
Immunoglobulins
Interleukins
Phytohemagglutinins
Immunoglobulin E
Interferon-gamma
Adenosine Deaminase