|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 October 2000, Vol. 96, No. 8, pp. 2803-2807
IMMUNOBIOLOGY
A partial deficiency of interleukin-7R is sufficient to
abrogate T-cell development and cause severe combined
immunodeficiency
Chaim M. Roifman,
Junyan Zhang,
David Chitayat, and
Nigel Sharfe
From the Divisions of Immunology/Allergy and Clinical
Genetics, Department of Paediatrics, The Infection, Immunity, Injury
and Repair Program, Research Institute, The Hospital for Sick Children
and The University of Toronto, Canada.
Both in vitro and in vivo studies established that interleukin 7 (IL-7) is essential for differentiation of immature T cells and B cells
but not natural killer (NK) cells in the mouse. In humans, although
both T-cell and B-cell progenitors express the functional IL-7 receptor
that consists of IL-7R and the  common (c) chain, this
lymphocyte receptor system is critical for T lineage but not for B
lineage development. Indeed, complete c deficiency like IL-7R
deficiency results in the arrest of T-cell but not B-cell development
(T B+ SCID). However, partial deficiency of
c caused by missense mutations results in a
T+B+ phenotype and a delay of clinical
presentation. It was therefore plausible to assume that partial
deficiency of IL-7R, like partial c deficiency may lead to a
milder clinical and immunologic phenotype. A P132S mutation in the
IL-7R was identified in 3 patients with severe combined
immunodeficiency (SCID) within an extensively consanguineous family.
Substitution of proline with serine in the extracellular portion of
IL-7R did not affect IL-7R messenger RNA (mRNA) and protein
expression, but severely compromised affinity to IL-7, resulting in
defective signal transduction. In response to IL-7 stimulation, Jak-3
phosphorylation was markedly reduced in both patient cells as well as
in COS cells reconstituted with mutant IL-7R. Surprisingly, this
partial deficiency of IL-7R resulted in a severe phenotype,
including markedly reduced circulating T cells while sparing B-cell
numbers similar to c chain deficiency. However, unlike the
previously reported cases, serum immunoglobulins were virtually absent.
Further, unlike c deficiency, NK cell numbers and function was
preserved. Despite the partial deficiency, clinical presentation was
indistinguishable from a complete c deficiency, including severe and
persistent viral and protozoal infections and failure to thrive. Unlike
partial c deficiency, a partial deficiency of IL-7R results in an
arrest of T-cell development, leading to typical severe combined
immunodeficiency. This underscores the critical role of IL-7R chain
in the differentiation of T cells.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. K. Parrish, I. Baez, T.-A. Milford, A. Benitez, N. Galloway, J. W. Rogerio, E. Sahakian, M. Kagoda, G. Huang, Q.-L. Hao, et al.
IL-7 Dependence in Human B Lymphopoiesis Increases during Progression of Ontogeny from Cord Blood to Bone Marrow
J. Immunol.,
April 1, 2009;
182(7):
4255 - 4266.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Faller, J. Kakal, R. Kumar, and P. MacPherson
IL-7 and the HIV Tat protein act synergistically to down-regulate CD127 expression on CD8 T cells
Int. Immunol.,
March 1, 2009;
21(3):
203 - 216.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. W. Kuijpers, P. A. Baars, C. Dantin, M. van den Burg, R. A. W. van Lier, and E. Roosnek
Human NK cells can control CMV infection in the absence of T cells
Blood,
August 1, 2008;
112(3):
914 - 915.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M.-L. Baron, D. Gauchat, R. La Motte-Mohs, N. Kettaf, A. Abdallah, T. Michiels, J.-C. Zuniga-Pflucker, and R.-P. Sekaly
TLR Ligand-Induced Type I IFNs Affect Thymopoiesis
J. Immunol.,
June 1, 2008;
180(11):
7134 - 7146.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Roberts, J. P. H. Lauritsen, M. Cooney, R. E. Parrott, E. O. Sajaroff, C. M. Win, M. D. Keller, J. H. Carpenter, J. Carabana, M. S. Krangel, et al.
T-B+NK+ severe combined immunodeficiency caused by complete deficiency of the CD3{zeta} subunit of the T-cell antigen receptor complex
Blood,
April 15, 2007;
109(8):
3198 - 3206.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Al-Tamemi, B. Mazer, D. Mitchell, P. Albuquerque, A. M. V. Duncan, C. McCusker, and N. Jabado
Complete DiGeorge Anomaly in the Absence of Neonatal Hypocalcemia and Velofacial and Cardiac Defects
Pediatrics,
September 1, 2005;
116(3):
e457 - e460.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. Zubkova, H. Mostowski, and M. Zaitseva
Up-Regulation of IL-7, Stromal-Derived Factor-1{alpha}, Thymus-Expressed Chemokine, and Secondary Lymphoid Tissue Chemokine Gene Expression in the Stromal Cells in Response to Thymocyte Depletion: Implication for Thymus Reconstitution
J. Immunol.,
August 15, 2005;
175(4):
2321 - 2330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Holm, P. Aukrust, J. K. Damas, F. Muller, B. Halvorsen, and S. S. Froland
Abnormal interleukin-7 function in common variable immunodeficiency
Blood,
April 1, 2005;
105(7):
2887 - 2890.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q. Jiang, W. Q. Li, R. R. Hofmeister, H. A. Young, D. R. Hodge, J. R. Keller, A. R. Khaled, and S. K. Durum
Distinct Regions of the Interleukin-7 Receptor Regulate Different Bcl2 Family Members
Mol. Cell. Biol.,
July 15, 2004;
24(14):
6501 - 6513.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Lum, D. J. Schnepple, Z. Nie, J. Sanchez-Dardon, G. L. Mbisa, J. Mihowich, N. Hawley, S. Narayan, J. E. Kim, D. H. Lynch, et al.
Differential Effects of Interleukin-7 and Interleukin-15 on NK Cell Anti-Human Immunodeficiency Virus Activity
J. Virol.,
June 1, 2004;
78(11):
6033 - 6042.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. E. Muller-Sieburg, R. H. Cho, L. Karlsson, J.-F. Huang, and H. B. Sieburg
Myeloid-biased hematopoietic stem cells have extensive self-renewal capacity but generate diminished lymphoid progeny with impaired IL-7 responsiveness
Blood,
June 1, 2004;
103(11):
4111 - 4118.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Laouar, I. N. Crispe, and R. A. Flavell
Overexpression of IL-7R{alpha} provides a competitive advantage during early T-cell development
Blood,
March 15, 2004;
103(6):
1985 - 1994.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Roberts, A. Lengi, S. M. Brown, M. Chen, Y.-J. Zhou, J. J. O'Shea, and R. H. Buckley
Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation
Blood,
March 15, 2004;
103(6):
2009 - 2018.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mestas and C. C. W. Hughes
Of Mice and Not Men: Differences between Mouse and Human Immunology
J. Immunol.,
March 1, 2004;
172(5):
2731 - 2738.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. Barata, V. A. Boussiotis, J. A. Yunes, A. A. Ferrando, L. A. Moreau, J. P. Veiga, S. E. Sallan, A. T. Look, L. M. Nadler, and A. A. Cardoso
IL-7-dependent human leukemia T-cell line as a valuable tool for drug discovery in T-ALL
Blood,
March 1, 2004;
103(5):
1891 - 1900.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Raza, G. N. Fuller, C. H. Rhee, S. Huang, K. Hess, W. Zhang, and R. Sawaya
Identification of Necrosis-Associated Genes in Glioblastoma by cDNA Microarray Analysis
Clin. Cancer Res.,
January 1, 2004;
10(1):
212 - 221.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. K. Dadi, A. J. Simon, and C. M. Roifman
Effect of CD3{delta} Deficiency on Maturation of {alpha}/{beta} and {gamma}/{delta} T-Cell Lineages in Severe Combined Immunodeficiency
N. Engl. J. Med.,
November 6, 2003;
349(19):
1821 - 1828.
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Storek, T. Gillespy III, H. Lu, A. Joseph, M. A. Dawson, M. Gough, J. Morris, R. C. Hackman, P. A. Horn, G. E. Sale, et al.
Interleukin-7 improves CD4 T-cell reconstitution after autologous CD34 cell transplantation in monkeys
Blood,
May 15, 2003;
101(10):
4209 - 4218.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. Barata, A. A. Cardoso, L. M. Nadler, and V. A. Boussiotis
Interleukin-7 promotes survival and cell cycle progression of T-cell acute lymphoblastic leukemia cells by down-regulating the cyclin-dependent kinase inhibitor p27kip1
Blood,
September 1, 2001;
98(5):
1524 - 1531.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. A. Reche, V. Soumelis, D. M. Gorman, T. Clifford, M.-r. Liu, M. Travis, S. M. Zurawski, J. Johnston, Y.-J. Liu, H. Spits, et al.
Human Thymic Stromal Lymphopoietin Preferentially Stimulates Myeloid Cells
J. Immunol.,
July 1, 2001;
167(1):
336 - 343.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
