Herpes virus saimiri transformation of T cells in CD3γ immunodeficiency: phenotypic and functional characterization

The characterization of T cell immunodeficiencies could in part be supported by using stable cell lines in which biochemical and molecular studies of the defect could be carried out thereby omitting frequent bleeding of patients. First attempts to obtain such cell lines included HTLV-I transformatio...

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Veröffentlicht in:Journal of immunological methods 1996-11, Vol.198 (2), p.177-186
Hauptverfasser: Rodríguez-Gallego, Carlos, Corell, Alfredo, Pacheco, Alberto, Timón, Marcos, Regueiro, JoséR., Allende, Luis M., Madroño, Agustín, Arnaiz-Villena, Antonio
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container_end_page 186
container_issue 2
container_start_page 177
container_title Journal of immunological methods
container_volume 198
creator Rodríguez-Gallego, Carlos
Corell, Alfredo
Pacheco, Alberto
Timón, Marcos
Regueiro, JoséR.
Allende, Luis M.
Madroño, Agustín
Arnaiz-Villena, Antonio
description The characterization of T cell immunodeficiencies could in part be supported by using stable cell lines in which biochemical and molecular studies of the defect could be carried out thereby omitting frequent bleeding of patients. First attempts to obtain such cell lines included HTLV-I transformation and exogenous IL-2 administration, but both models have important disadvantages. Recently, a virus isolated from the squirrel monkey, Herpes virus saimiri (HVS), has been reported to have the ability to transform T cells. A stable IL-2-dependent HVS-transformed T cell line from a CD3γ deficient patient has been obtained; and this cell line displays both the phenotypic and the functional characteristics of the patient's lymphocytes. Moreover, the line down-modulates TCR CD3 surface expression upon CD3 engagement, as do the patient's lymphocytes, showing that CD3γ and its phosphorylation are not necessary for TCR CD3 internalization. In addition, the abnormal staining pattern of different anti- TCR CD3 monoclonal antibodies is preserved in the HVS-patient line. Since HVS is capable of transforming CD3 γ − T cells, the CD3γ chain does not seem to be involved in the HVS receptor process. The fact that it is not possible to obtain a CD8 + HVS line from the CD3 γ − patient supports the existence of a functional anomaly in his scanty CD8 + peripheral lymphocytes. Thus, HVS transformation is a suitable model for T cell immunodeficiency studies and characterization. It may also be used in the future in cellular models for in vitro gene therapy trials.
doi_str_mv 10.1016/S0022-1759(96)00156-1
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First attempts to obtain such cell lines included HTLV-I transformation and exogenous IL-2 administration, but both models have important disadvantages. Recently, a virus isolated from the squirrel monkey, Herpes virus saimiri (HVS), has been reported to have the ability to transform T cells. A stable IL-2-dependent HVS-transformed T cell line from a CD3γ deficient patient has been obtained; and this cell line displays both the phenotypic and the functional characteristics of the patient's lymphocytes. Moreover, the line down-modulates TCR CD3 surface expression upon CD3 engagement, as do the patient's lymphocytes, showing that CD3γ and its phosphorylation are not necessary for TCR CD3 internalization. In addition, the abnormal staining pattern of different anti- TCR CD3 monoclonal antibodies is preserved in the HVS-patient line. Since HVS is capable of transforming CD3 γ − T cells, the CD3γ chain does not seem to be involved in the HVS receptor process. The fact that it is not possible to obtain a CD8 + HVS line from the CD3 γ − patient supports the existence of a functional anomaly in his scanty CD8 + peripheral lymphocytes. Thus, HVS transformation is a suitable model for T cell immunodeficiency studies and characterization. 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First attempts to obtain such cell lines included HTLV-I transformation and exogenous IL-2 administration, but both models have important disadvantages. Recently, a virus isolated from the squirrel monkey, Herpes virus saimiri (HVS), has been reported to have the ability to transform T cells. A stable IL-2-dependent HVS-transformed T cell line from a CD3γ deficient patient has been obtained; and this cell line displays both the phenotypic and the functional characteristics of the patient's lymphocytes. Moreover, the line down-modulates TCR CD3 surface expression upon CD3 engagement, as do the patient's lymphocytes, showing that CD3γ and its phosphorylation are not necessary for TCR CD3 internalization. In addition, the abnormal staining pattern of different anti- TCR CD3 monoclonal antibodies is preserved in the HVS-patient line. Since HVS is capable of transforming CD3 γ − T cells, the CD3γ chain does not seem to be involved in the HVS receptor process. The fact that it is not possible to obtain a CD8 + HVS line from the CD3 γ − patient supports the existence of a functional anomaly in his scanty CD8 + peripheral lymphocytes. Thus, HVS transformation is a suitable model for T cell immunodeficiency studies and characterization. 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The fact that it is not possible to obtain a CD8 + HVS line from the CD3 γ − patient supports the existence of a functional anomaly in his scanty CD8 + peripheral lymphocytes. Thus, HVS transformation is a suitable model for T cell immunodeficiency studies and characterization. It may also be used in the future in cellular models for in vitro gene therapy trials.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>8946013</pmid><doi>10.1016/S0022-1759(96)00156-1</doi><tpages>10</tpages></addata></record>
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identifier ISSN: 0022-1759
ispartof Journal of immunological methods, 1996-11, Vol.198 (2), p.177-186
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1872-7905
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subjects [formula omitted] modulation
AIDS/HIV
CD3 Complex - analysis
CD3 Complex - genetics
Cell Line, Transformed
Cell Transformation, Viral - immunology
Flow Cytometry
Herpesvirus 2, Saimiriine - immunology
herpesvirus saimiri
Humans
Immunologic Deficiency Syndromes - immunology
Immunophenotyping
Lymphocyte Activation
T cell defect
T cell immortalization
T cell line
T lymphocyte
T-Lymphocytes - immunology
T-Lymphocytes - virology
title Herpes virus saimiri transformation of T cells in CD3γ immunodeficiency: phenotypic and functional characterization
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