Transformation of human T-cell clones by Herpesvirus saimiri: intact antigen recognition by autonomously growing myelin basic protein-specific T cells.
Herpesvirus saimiri has recently been shown to immortalize human T cells. It was unknown, however, whether Herpesvirus saimiri transformation affects T-cell receptor (TCR) expression and signal transduction. In the present study, we have transformed CD4+ human T-cell clones specific for human myelin basic protein. The transformed T cells were grown in interleukin 2 and divided in the absence of antigen and antigen-presenting cells. They retained the membrane phenotype of activated T cells and secreted the cytokines interferon gamma and lymphotoxin, but interleukin 4 was not detected. Further, the transformed T cells continued to express the original TCR as demonstrated by TCR variable-region-V beta-specific monoclonal antibodies and TCR sequencing. Antigen-specific recognition and signal transduction by the TCR were demonstrated by myelin-basic-protein-induced HLA-DR-restricted secretion of interferon gamma and lymphotoxin and by myelin-basic-protein-specific proliferation. Antigen specificity and reactivity have been maintained for > 1 year after transformation. Transformation with Herpesvirus saimiri now allows the production of virtually unlimited numbers of (auto)antigen-specific T cells expressing functional TCR and a stable membrane phenotype. This technology will facilitate studies of the pathogenesis of putative autoimmune diseases, such as multiple sclerosis, and may be of help in TCR-targeted immunotherapy.
Weber
F
F
Department of Neuroimmunology, Max Planck Institute of Psychiatry, Martinsried, Germany.
Meinl
E
E
Drexler
K
K
Czlonkowska
A
A
Huber
S
S
Fickenscher
H
H
Müller-Fleckenstein
I
I
Fleckenstein
B
B
Wekerle
H
H
Hohlfeld
R
R
D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001483:Base Sequence; D018801:CD2 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000382:microbiology; D018968:CD58 Antigens; D002472:Cell Transformation, Viral; D016207:Cytokines / Q000096:biosynthesis; D017931:DNA Primers / Q000737:chemistry; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics*; D006801:Humans; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011971:Receptors, Immunologic / Q000378:metabolism
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D018968:CD58 Antigens; D016207:Cytokines; D017931:DNA Primers; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic