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Familial NK cell deficiency associated with impaired IL-2- and IL-15-dependent survival of lymphocytes.
- 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.
- Subjects :
- Adolescent
Apoptosis drug effects
Case-Control Studies
Child
Child, Preschool
Family Health
Female
Humans
Infant
Lymphopenia etiology
Cell Survival drug effects
Immunologic Deficiency Syndromes etiology
Interleukin-15 pharmacology
Interleukin-2 pharmacology
Killer Cells, Natural pathology
Lymphocytes pathology
Subjects
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