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Familial NK cell deficiency associated with impaired IL-2- and IL-15-dependent survival of lymphocytes.

Authors :
Eidenschenk C
Jouanguy E
Alcaïs A
Mention JJ
Pasquier B
Fleckenstein IM
Puel A
Gineau L
Carel JC
Vivier E
Le Deist F
Casanova JL
Source :
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2006 Dec 15; Vol. 177 (12), pp. 8835-43.
Publication Year :
2006

Abstract

We previously reported the clinical phenotype of two siblings with a novel inherited developmental and immunodeficiency syndrome consisting of severe intrauterine growth retardation and the impaired development of specific lymphoid lineages, including transient CD8 alphabeta T lymphopenia and a persistent lack of blood NK cells. We describe here the elucidation of a plausible underlying pathogenic mechanism, with a cellular phenotype of impaired survival of both fresh and herpesvirus saimiri-transformed T cells, in the surviving child. Clearly, NK cells could not be studied. However, peripheral blood T lymphocytes displayed excessive apoptosis ex vivo. Moreover, the survival rates of CD4 and CD8 alphabeta T cell blasts generated in vitro, and herpesvirus saimiri-transformed T cells cultured in vitro, were low, but not nil, following treatment with IL-2 and IL-15. In contrast, Fas-mediated activation-induced cell death was not enhanced, indicating a selective excess of cytokine deprivation-mediated apoptosis. In keeping with the known roles of IL-2 and IL-15 in the development of NK and CD8 T cells in the mouse model, these data suggest that an impaired, but not abolished, survival response to IL-2 and IL-15 accounts for the persistent lack of NK cells and the transient CD8 alphabeta T lymphopenia documented in vivo. Impaired cytokine-mediated lymphocyte survival is likely to be the pathogenic mechanism underlying this novel form of inherited and selective NK deficiency in humans.

Details

Language :
English
ISSN :
0022-1767
Volume :
177
Issue :
12
Database :
MEDLINE
Journal :
Journal of immunology (Baltimore, Md. : 1950)
Publication Type :
Academic Journal
Accession number :
17142786
Full Text :
https://doi.org/10.4049/jimmunol.177.12.8835