|
|
 Previous Article | Table of Contents | Next Article 
gamma-c gene transfer into SCID X1 patients' B-cell lines restores normal
high-affinity interleukin-2 receptor expression and function
H Hacein-Bey, M Cavazzana-Calvo, F Le Deist, A Dautry-Varsat, C Hivroz, I Riviere, O Danos, JM Heard, K Sugamura, A Fischer and G De Saint Basile
Institut National de la Sante et de la Recherche Medicale U429, Hopital
Necker-Enfants Malades, Paris, France.
SCID X1 is characterized by faulty T-cell and natural killer cell
differentiation caused by mutation of the gamma-c chain gene encoding a
number of multiple cytokine receptors (interleukin-2 [IL-2], IL-4, IL- 7,
IL-9, and IL-15 receptors). To assess the feasibility of inducing long-term
expression and function of the gamma-c chain, Epstein-Barr virus
(EBV)-transformed B-cell lines from two patients with SCID X1 were
transduced with a Moloney-derived retroviral vector containing the gamma-c
chain cDNA. The viral LTR was used as the promoter. Immediately after two
cycles of coculture with the psi-crip clone producing the MFG(B2)-gamma-c
cDNA vector, gamma-c expression, assessed by detection of the mRNA and
membrane protein expression, was found in 15% to 20% of cells. The degree
of membrane expression was similar to that in control EBV-B cells.
Expression increased steadily over 6 months, becoming detectable in 100% of
cells, and remained stable thereafter for a total of 9 months, reflecting
positive selection of transduced cells. A study of provirus integration
sites showed multiple integration. The expressed gamma-c was functional,
because it restored high-affinity IL- 2 receptor binding, IL-2 endocytosis,
and IL-2-triggered phosphorylation of JAK-3 tyrosine kinase. Similar
results were obtained with the two B-cell lines. These results show that
efficient gamma-c gene transfer into B-cells lacking functional gamma-c is
feasible and results in strong and stable expression of a functional
gamma-c chain, apparently conferring a selective growth advantage in
culture. Further in vitro studies of gamma-c gene transfer into gamma-c-
hematopoietic progenitors are being conducted to assess the feasibility of
correcting lymphocyte differentiation defects.
Volume 87,
Issue 8,
pp. 3108-3116,
04/15/1996
Copyright © 1996 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
C. Lagresle-Peyrou, F. Yates, M. Malassis-Seris, C. Hue, E. Morillon, A. Garrigue, A. Liu, P. Hajdari, D. Stockholm, O. Danos, et al.
Long-term immune reconstitution in RAG-1-deficient mice treated by retroviral gene therapy: a balance between efficiency and toxicity
Blood,
January 1, 2006;
107(1):
63 - 72.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hacein-Bey-Abina, C. Von Kalle, M. Schmidt, M. P. McCormack, N. Wulffraat, P. Leboulch, A. Lim, C. S. Osborne, R. Pawliuk, E. Morillon, et al.
LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1
Science,
October 17, 2003;
302(5644):
415 - 419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. D. Cooper, L. L. Lanier, M. E. Conley, and J. M. Puck
Immunodeficiency Disorders
Hematology,
January 1, 2003;
2003(1):
314 - 330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. J. Tsai, H. L. Malech, M. R. Kirby, A. P. Hsu, N. E. Seidel, C. D. Porada, E. D. Zanjani, D. M. Bodine, and J. M. Puck
Retroviral transduction of IL2RG into CD34+ cells from X-linked severe combined immunodeficiency patients permits human T- and B-cell development in sheep chimeras
Blood,
June 17, 2002;
100(1):
72 - 79.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. May, S. Rivella, A. Chadburn, and M. Sadelain
Successful treatment of murine beta -thalassemia intermedia by transfer of the human beta -globin gene
Blood,
March 15, 2002;
99(6):
1902 - 1908.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Bani, V. Pasquier, M. Kryworuchko, J. Salamero, and J. Theze
Unstimulated Human CD4 Lymphocytes Express a Cytoplasmic Immature Form of the Common Cytokine Receptor {{gamma}}-Chain
J. Immunol.,
July 1, 2001;
167(1):
344 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Otsu, K. Sugamura, and F. Candotti
Lack of dominant-negative effects of a truncated {gamma}c on retroviral-mediated gene correction of immunodeficient mice
Blood,
March 15, 2001;
97(6):
1618 - 1624.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Soudais, T. Shiho, L. I. Sharara, D. Guy-Grand, T. Taniguchi, A. Fischer, and J. P. Di Santo
Stable and functional lymphoid reconstitution of common cytokine receptor gamma chain deficient mice by retroviral-mediated gene transfer
Blood,
May 15, 2000;
95(10):
3071 - 3077.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Cavazzana-Calvo, S. Hacein-Bey, G. d. S. Basile, F. Gross, E. Yvon, P. Nusbaum, F. Selz, C. Hue, S. Certain, J. Casanova, et al.
Gene Therapy of Human Severe Combined Immunodeficiency (SCID)-X1 Disease
Science,
April 28, 2000;
288(5466):
669 - 672.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
M. Lo, M. L. Bloom, K. Imada, M. Berg, J. M. Bollenbacher, E. T. Bloom, B. L. Kelsall, and W. J. Leonard
Restoration of Lymphoid Populations in a Murine Model of X-Linked Severe Combined Immunodeficiency by a Gene-Therapy Approach
Blood,
November 1, 1999;
94(9):
3027 - 3036.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hacein-Bey, G. D. S. Basile, J. Lemerle, A. Fischer, and M. Cavazzana-Calvo
gamma c Gene Transfer in the Presence of Stem Cell Factor, FLT-3L, Interleukin-7 (IL-7), IL-1alpha , and IL-15 Cytokines Restores T-Cell Differentiation From gamma c(-) X-Linked Severe Combined Immunodeficiency Hematopoietic Progenitor Cells in Murine Fetal Thymic Organ Cultures
Blood,
December 1, 1998;
92(11):
4090 - 4097.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Whitwam, M. E. Haskins, P. S. Henthorn, J. N. Kraszewski, S. E. Kleiman, N. E. Seidel, D. M. Bodine, and J. M. Puck
Retroviral Marking of Canine Bone Marrow: Long-Term, High-Level Expression of Human Interleukin-2 Receptor Common Gamma Chain in Canine Lymphocytes
Blood,
September 1, 1998;
92(5):
1565 - 1575.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. David, L. Bani, J.-L. Moreau, C. Demaison, K. Sun, O. Salvucci, T. Nakarai, M. de Montalembert, S. Chouaib, M. Joussemet, et al.
Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets
Blood,
January 1, 1998;
91(1):
165 - 172.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Puck, A. E. Pepper, P. S. Henthorn, F. Candotti, J. Isakov, T. Whitwam, M. E. Conley, R. E. Fischer, H. M. Rosenblatt, T. N. Small, et al.
Mutation Analysis of IL2RG in Human X-Linked Severe Combined Immunodeficiency
Blood,
March 15, 1997;
89(6):
1968 - 1977.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
