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Published online before print February 22, 2005

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0904500

Received for publication September 8, 2004.
Revised December 30, 2004.
Accepted for publication January 24, 2005.

Article

Herpesvirus saimiri-transformed CD8⁺ T cells as a tool to study Chediak-Higashi syndrome cytolytic lymphocytes

José M. Martín-Fernández ^*, Juan A. Cabanillas ^*, Miguel Rivero-Carmena ^*, Esther Lacasa , Julián Pardo , Alberto Anel , Pedro R. Ramírez-Duque , Fernando Merino , Carlos Rodríguez-Gallego ^¶, and José R. Regueiro ^*@

*Inmunología, Facultad de Medicina, Universidad Complutense, Madrid, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Facultad de Ciencias, Universidad de Zaragoza, Spain; Hematología, Hospital Central, Tachira, Venezuela; Fisiología, Facultad de Medicina y Odontología, Universidad del País Vasco, Bilbao, Spain; and ^¶Inmunología, Hospital de Gran Canaria, Las Palmas, Spain

^@ To whom correspondence should be addressed. E-mail: regueiro{at}med.ucm.es.

	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.

Key Words: T lymphocyte • immunodeficiency diseases • cytolytic cells

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