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Title: Herpesvirus saimiri-transformed CD8<sup>+</sup>T cells as a tool to study Chediak-Higashi syndrome cytolytic lymphocytes
Authors: Martín-Fernández, José M.
Cabanillas, Juan A.
Rivero-Carmena, Miguel
Lacasa, Esther
Pardo, Julián
Anel, Alberto
Ramírez-Duque, Pedro R.
Merino, Fernando
Rodríguez-Gallego, Carlos 
Regueiro, José R.
UNESCO Clasification: 32 Ciencias médicas
3205 Medicina interna
Keywords: T lymphocyte
Immunodeficiency diseases
Cytolytic cell
Issue Date: 2005
Journal: Journal of Leukocyte Biology 
Abstract: Cytolytic CD8+ T lymphocytes are the main cell type involved in the fatal lymphoproliferative-accelerated phase of the Chediak-Higashi syndrome (CHS). To generate a cellular tool to study the defects of this T cell subset in vitro, we have used Herpesvirus saimiri, a lymphotropic virus that transforms human T lymphocytes into extended growth and in addition, endows them with natural killer (NK) features. Transformed CHS CD8+ T cells were generated and characterized in comparison with healthy controls. The results showed that transformed CHS T cells maintained the defects described in primary CHS lymphocytes, such as giant secretory lysosomes and impaired NK and T cell receptor/CD3-induced, perforin-mediated cytolytic activity [which, however, could be restored after extended culture in the presence of interleukin-2 (IL-2)]. Upon activation with phorbol ester plus calcium ionophore or upon extended culture with IL-2, transformed CHS T cells showed normal, perforin-independent plasma membrane CD178/CD95L/FasL-mediated cytolytic activity but negligible secretion of microvesicle-bound CD95L. Transformed (and primary) CHS T cells were otherwise normal for cytolysis-independent activation functions, such as proliferation, surface expression of several activation markers including major histocompatibility complex class II, and cytokine or surface activation-marker induction. Therefore, the CHS protein [CHS1/LYST (for lysosomal traffic regulator)] can be dispensable for certain NK and T cell cytolytic activities of activated CHS CD8+ T lymphocytes, but it seems to be required for microvesicle secretion of CD95L. We conclude that transformed CHS T cells may be useful as a tool to study in vitro the relative role of CHS1/LYST in NK and T lymphocyte cytolysis and antigen presentation.
ISSN: 0741-5400
DOI: 10.1189/jlb.0904500
Source: Journal of Leukocyte Biology[ISSN 0741-5400],v. 77, p. 661-668 (Mayo 2005)
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