부산대학교 도서관

During an immune response, [CD8.sup.+] T lymphocytes can undergo asymmetric division, giving rise to daughter cells that exhibit distinct tendencies to adopt terminal effector and memory cell fates. Here we show that "pre-effector" and "pre-memory" cells resulting from the first [CD8.sup.+] T cell division in vivo exhibited low and high rates of endogenous proteasome activity, respectively. Pharmacologic reduction of proteasome activity in [CD8.sup.+] T cells early during differentiation resulted in acquisition of terminal effector cell characteristics, whereas enhancement of proteasome activity conferred attributes of memory lymphocytes. Transcriptomic and proteomic analyses revealed that modulating proteasome activity in [CD8.sup.+] T cells affected cellular metabolism. These metabolic changes were mediated, in part, through differential expression of Myc, a transcription factor that controls glycolysis and metabolic reprogramming. Taken together, these results demonstrate that proteasome activity is an important regulator of [CD8.sup.+] T cell fate and raise the possibility that increasing proteasome activity may be a useful therapeutic strategy to enhance the generation of memory lymphocytes.
Introduction In response to microbial infection, [CD8.sup.+] T lymphocytes undergo rapid clonal proliferation associated with differentiation into terminal effector and memory cell subsets. Terminally differentiated, short-lived effector cells produce inflammatory [...]