Cell division predicts CD62L expression in vivo (83.6)

Abstract

Abstract Naïve CD8+ T cells express a predominantly CD62Lhigh phenotype, but CD62L expression is rapidly lost during the effector phase of the immune response and only slowly regained during the memory phase. We used adoptive transfer of TCR-transgenic T cells followed by Listeria infection to study the dynamics of cell division and differentiation in vivo. Adoptive transfer of larger quantities (400 000) of naïve TCR-transgenic T cells leads to diminished T cell growth following infection and a higher proportion of cells remaining CD62Lhigh than populations derived from adoptive transfer populations of smaller quantities (3200 naïve TCR-tg T cells). This suggests a process of 'division-linked differentiation', where a proportion of cells change phenotype (in this case CD62Lhigh => CD62Llow) upon division. A simple model of division-linked CD62L differentiation where 20% of CD62Lhigh cells differentiate to become CD62Llow on each division accurately predicts the phenotype of cells during acute infection. By contrast, expression of CD127 did not conform to this simple pattern of differentiation. These results suggests that CD62Lhigh and CD62Llow cells arise from the same precursors, and CD62Llow cells are formed from the CD62Lhigh population by a process of progressive, division-linked differentiation.