|
|
 Previous Article | Table of Contents | Next Article 
A primary T-cell immunodeficiency associated with defective transmembrane
calcium influx
F Le Deist, C Hivroz, M Partiseti, C Thomas, HA Buc, M Oleastro, B Belohradsky, D Choquet and A Fischer
INSERM U132, Hopital Necker Enfants Malades, Paris, France.
We investigated a T-cell activation deficiency in a 3-month-old boy with
protracted diarrhea, serious cytomegalovirus pneumonia, and a family
history (in a brother) of cytomegalovirus infection and toxoplasmosis. In
spite of detection of normal number of peripheral lymphocytes, T cells did
not proliferate after activation by anti-CD3 and anti-CD2 antibodies,
although proliferation induced by antigens was detectable. We sought to
determine the origin of this defect as it potentially represented a
valuable tool to analyze T-cell physiology. T- cell activation by anti-CD3
antibody or phytohemagglutinin (PHA) led to reduced interleukin-2 (IL-2)
production and abnormal nuclear factor- activated T cell (NF-AT; a complex
regulating the IL-2 gene transcription) binding activity to a specific
oligonucleotide. T-cell proliferation was restored by IL-2. Early events of
T-cell activation, such as anti-CD3 antibody-induced cellular protein
tyrosine phosphorylation, p59fyn and p56lck kinase activities, and
phosphoinositide turnover, were found to be normal. In contrast, anti- CD3
antibody-induced Ca2+ flux was grossly abnormal. Release from endoplasmic
reticulum stores was detectable as tested in the presence of anti-CD3
antibody or thapsigargin after cell membrane depolarization in a K+ rich
medium, whereas extracellular entry of Ca2+ was defective. The latter
abnormality was not secondary to defective K+ channel function, which was
found to be normal. A similar defect was found in other hematopoietic cell
lineages and in fibroblasts as evaluated by both cytometry and digital
video imaging experiments at a single-cell level. This primary T-cell
immunodeficiency appears, thus, to be due to defective Ca2+ entry through
the plasma membrane. The same abnormality did not alter B-cell
proliferation, platelet function, and polymorphonuclear neutrophil (PMN)
function. Elucidation of the mechanism underlying this defect would help to
understand the physiology of Ca2+ mobilization in T cells.
Volume 85,
Issue 4,
pp. 1053-1062,
02/15/1995
Copyright © 1995 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:
|
|
|
|
 
Y. Gwack, S. Srikanth, M. Oh-hora, P. G. Hogan, E. D. Lamperti, M. Yamashita, C. Gelinas, D. S. Neems, Y. Sasaki, S. Feske, et al.
Hair Loss and Defective T- and B-Cell Function in Mice Lacking ORAI1
Mol. Cell. Biol.,
September 1, 2008;
28(17):
5209 - 5222.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Oakes
Mitochondria control calcium entry at the immunological synapse
PNAS,
September 25, 2007;
104(39):
15171 - 15172.
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. P. Carroll, B. B.A. McNaull, and M. Gadina
Immunodeficiency Is A Tough Nut to CRAC: The Importance of Calcium Flux in T Cell Activation.
Mol. Interv.,
October 1, 2006;
6(5):
253 - 256.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Yan, J. Xing, C. Lorin-Nebel, A. Y. Estevez, K. Nehrke, T. Lamitina, and K. Strange
Function of a STIM1 Homologue in C. elegans: Evidence that Store-operated Ca2+ Entry Is Not Essential for Oscillatory Ca2+ Signaling and ER Ca2+ Homeostasis
J. Gen. Physiol.,
October 1, 2006;
128(4):
443 - 459.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Feske, M. Prakriya, A. Rao, and R. S. Lewis
A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients
J. Exp. Med.,
September 6, 2005;
202(5):
651 - 662.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Q.-H. Liu, X. Liu, Z. Wen, B. Hondowicz, L. King, J. Monroe, and B. D. Freedman
Distinct Calcium Channels Regulate Responses of Primary B Lymphocytes to B Cell Receptor Engagement and Mechanical Stimuli
J. Immunol.,
January 1, 2005;
174(1):
68 - 79.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Zitt, B. Strauss, E. C. Schwarz, N. Spaeth, G. Rast, A. Hatzelmann, and M. Hoth
Potent Inhibition of Ca2+ Release-activated Ca2+ Channels and T-lymphocyte Activation by the Pyrazole Derivative BTP2
J. Biol. Chem.,
March 26, 2004;
279(13):
12427 - 12437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Schwarz, E. Tutsch, B. Ludwig, E. C. Schwarz, A. Stallmach, and M. Hoth
Ca2+ Signaling in Identified T-lymphocytes from Human Intestinal Mucosa: RELATION TO HYPOREACTIVITY, PROLIFERATION, AND INFLAMMATORY BOWEL DISEASE
J. Biol. Chem.,
February 13, 2004;
279(7):
5641 - 5647.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Philipp, B. Strauss, D. Hirnet, U. Wissenbach, L. Mery, V. Flockerzi, and M. Hoth
TRPC3 Mediates T-cell Receptor-dependent Calcium Entry in Human T-lymphocytes
J. Biol. Chem.,
July 11, 2003;
278(29):
26629 - 26638.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hacein-Bey-Abina, F. Le Deist, F. Carlier, C. Bouneaud, C. Hue, J.-P. De Villartay, A. J. Thrasher, N. Wulffraat, R. Sorensen, S. Dupuis-Girod, et al.
Sustained Correction of X-Linked Severe Combined Immunodeficiency by ex Vivo Gene Therapy
N. Engl. J. Med.,
April 18, 2002;
346(16):
1185 - 1193.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. W. Putney Jr.
Pharmacology of Capacitative Calcium Entry
Mol. Interv.,
June 1, 2001;
1(2):
84 - 94.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.-O. Hueber, M. Zornig, A.-M. Bernard, M. Chautan, and G. Evan
A Dominant Negative Fas-associated Death Domain Protein Mutant Inhibits Proliferation and Leads to Impaired Calcium Mobilization in Both T-cells and Fibroblasts
J. Biol. Chem.,
March 31, 2000;
275(14):
10453 - 10462.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Babnigg, S. R. Bowersox, and M. L. Villereal
The Role of pp60c-src in the Regulation of Calcium Entry via Store-operated Calcium Channels
J. Biol. Chem.,
November 21, 1997;
272(47):
29434 - 29437.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Boulay, X. Zhu, M. Peyton, M. Jiang, R. Hurst, E. Stefani, and L. Birnbaumer
Cloning and Expression of a Novel Mammalian Homolog of Drosophila Transient Receptor Potential (Trp) Involved in Calcium Entry Secondary to Activation of Receptors Coupled by the Gq Class of G Protein
J. Biol. Chem.,
November 21, 1997;
272(47):
29672 - 29680.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
