Dynamic programming of CD8+ T lymphocyte responses

Abstract

The initial encounter with an antigen-presenting cell (APC) is the primary force behind the expansion, differentiation and survival of naive T cells. Using an APC that permits temporal control of priming, we examined whether the duration of antigenic stimulation can influence the functional development of CD8+ cytotoxic T lymphocytes (CTLs) in vivo. Whereas CTLs given a 4-h stimulus underwent an abortive clonal expansion with transient surface CD25 expression, those given a 20-h stimulus sustained CD25 up-regulation, proliferated extensively, and efficiently mediated destruction of peripheral target tissues. Our results show that an instructional program preceding the first cell division integrates differences in signal strength into the decision to activate versus tolerize specific CTL clones.

Properties of murine CD8+CD27- T cells

“…This homing pattern correlated with down modulation of CD62L and CCR7 and stable expression of CD44 and CD49d [50]. In vivo and in vitro studies with CD8 + T cells showed that total signal strength determines functional outcome of differentiation and acquisition of "fitness" [42,[52][53][54]. In line with this, we suggest that T cells that have been triggered multiple times via strong TCR signaling plus costimulatory molecules like CD27 favor differentiation into "fit" effector [20] and memory T cells that ultimately no longer express CD27.…”

Potential killers exposed: tracking endogenous influenza‐specific CD8+ T cells

“…In particular, the cellular environment and the initial priming of naïve CD8 + T cells dictate the efficacy of recall responses, and therefore impact vaccine efficacy 7, 8, 9, 10. Analysis of the early events of IAV‐specific CD8 + T‐cell responses has been limited, in part because numbers of virus‐specific CD8 + T cells remain low during the initial stages following antigen encounter.…”

Expression and function of 4‐1BB during CD4 versus CD8 T cell responses in vivo

“…Whether this difference was due to in vivo versus in vitro stimulation or the nature of the stimulus was not clear. Within the first 20 h of stimulation, T cells receive the signals they need to undergo a pre-programmed expansion phase that appears to be independent of further T cell activation [33][34][35][36][37]. Recent evidence also suggests that CD8 T cells kill antigen-presenting DC during the first few days of the response [38].…”