Cytokine-driven immortalization of in vitro activated human T lymphocytes - CD28 expression correlates inversely with cell population doublings

Like other normal human somatic cells, T lymphocytes are believed to have a finite in vitro life span. However, continuous T lymphocyte cell lines can often be established from chronic inflammatory skin diseases when the culture medium is supplemented with IL-2 and IL-4 but without antigen and accessory cells added. Based on the assumption that these continuous T lymphocyte cell lines were activated by antigen during the chronic inflammation taking place in vivo, I investigated whether peripheral blood T lymphocytes could be induced to cytokine-dependent continuous growth following antigen activation. Upon allostimulation, peripheral blood CD4+ T lymphocytes reproducibly escape from cellular senescence. These IL-2- and IL-4-dependent continuous T cell lines show high telomerase activity. Withdrawal of either IL-2 or IL-4 results in cell growth arrest concomitant with down-regulation of telomerase activity. When cultured continuously, these CD4+ human T lymphocytes gradually lose expression of CD28.