Maintenance of normal T lymphocyte function after transfection with SV40 large T.
Human T lymphocytes in culture undergo cellular senescence similar to that observed in fibroblasts. We recently demonstrated that senescence of T lymphocytes can be postponed by transfection with SV40 large T. In the current study, we examine the functional activity of SV40 large T transfected T lymphocytes. Transfected T cells of both young and elderly subjects appear to display normal T cell function: they cease doubling upon removal of IL-2; in the presence of autologous adherent mononuclear cells they respond to mitogen stimulation and produce IL-2 and IFN-gamma during proliferation; and they express both IL-2 and transferrin receptors similar to those observed in mitogen-stimulated nontransfected T cells. In addition, more than 90% of the transfected cells express both the CD4 and "naive" T cell marker, CD45RA. In order to investigate whether the lack of long-lived CD8+ cells reflects phenotypic restriction, separated CD4+ and CD8+ subpopulations were transfected with SV40 large T. All transfections resulted in extended life spans of CD4+, but not CD8+, cells. Therefore, although SV40 large T transfected T lymphocytes maintain normal function, while demonstrating an extended life span, the effect may be restricted to CD4+ cells.
Department of Microbiology and Immunology, Medical College of Pennsylvania, Philadelphia 19129.
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Ryan
I M
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Goonewardene
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Murasko
D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D002469:Cell Separation; D002470:Cell Survival; D002472:Cell Transformation, Viral; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D011990:Receptors, Transferrin; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens