Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+ Th cells cytotoxic by activating both perforin- and FasL-pathways

During viral infection. CD8(+) cytotoxic T lymphocytes (CTL) play a central role to eliminate viruses by destructing virus-infected cells utilizing two cytolytic pathways, i.e., perforin/granzyme pathway and FasL-Fas pathway. It has been shown that effector functions of CTL are critically controlled by two T-box transcription factors, T-bet and eomesodermin (Eomes), although their precise activities in constructing CTL functions are not fully understood. To investigate the functional potency and activities of Eomes, the effects of ectopic expression of Eomes in two terminally differentiated murine CD4(+) Th lines, on their effector functions were analyzed. The results showed that in Eomes-transfected Th hybridoma, cell surface FasL expression upon Con A stimulation was markedly enhanced, although perforin expression was not induced. In normal, non-transformed Th2 cells, introduction of Eomes elicited perforin expression, and also augmented FasL up-regulation. Interestingly, cyotlytic activity of Eomes-transfectant was more efficient than that of perforin-transfected Th2 cells which expressed high levels of perforin and granzyme B mRNA, indicating that Eomes may play additional roles other than preparation of these cytolytic effector molecules. In contrast, stimulation-induced CD154 up-regulation, one of the typical helper T cell characteristics, was repressed in Eomes-transfectant. Collectively, these results suggest that Eomes may not only be involved in perforin/granzyme expression but also play various functions, including FasL up-regulation, to develop the characteristics of CD8(+) CTL These studies have also suggested that introduction of Eomes alone was sufficient to convert the functions of fully differentiated Th cells toward those of CTL (C) 2012 Elsevier B.V. All rights reserved.