Qin C. Ryan, I.Michael Goonewardene, Donna M. Murasko

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.