Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection

Abstract

In the present study, naive T cells were compared with in vivo generated effector and memory T cells expressing the same TCR specific for lymphocytic choriomeningitis virus. Upon restimulation in vitro, the same minimal concentrations of the full agonist peptide p33 and also of weak and partial agonist peptides were required for proliferation of naive, effector and memory T cells, indicating no difference in threshold of activation. However, activation ki-netics were distinct. While effector cytotoxic T cells exhibited immediate ex vivo lytic effector function, naive and memory T cells required 12 h and more exposure to antigen to develop lytic activity. However, both effector and memory T cells contained IFN-+ mRNA in vivo and required less than 3 h for secretion of cytokines upon restimulation in vitro. In contrast, naive T cells did not contain IFN-+ mRNA and required more than 12 h for cytokine secretion. Our results show that memory T cells exhibit a unique phenotype in that they produce cytokines and commit to proliferation as rapidly as effector cells, whereas they resemble naive T cells in the time requirement for development of cytolytic function.

Primary Human Lymphocytes Transduced with NY-ESO-1 Antigen-Specific TCR Genes Recognize and Kill Diverse Human Tumor Cell Lines

“…It is important to demonstrate functional avidity by cell lysis, because cytokine secretion and cytotoxicity are regulated independently in CD8 ϩ T cells (36,37). These results may have significant potential impact on the ability to treat cancer patients using adoptive immunotherapy.…”

A stochastic model of cytotoxic T cell responses

“…They probably have the same antigenic stimulation requirements as na. ıve cells (Bachmann et al, 1999;Kersh et al, 2003), although some studies found stimulation requirements to be lower (Pihlgren et al, 1996). Their replication rates are approximately the same as recently activated na.…”

“…Upon antigenic stimulation, memory cells begin to proliferate almost immediately and develop cytotoxicity within a few hours (Bachmann et al, 1999;Barber et al, 2003;Byers et al, 2003). They probably have the same antigenic stimulation requirements as na.…”

“…ıve cells except that we assume it takes only 1 h (t m =1 h) for a stimulated memory cell to begin its programmed response, reflecting the rapid response of memory cells to pathogens (Bachmann et al, 1999;Barber et al, 2003).…”

Hyperproliferative Response of a Monoclonal Memory CD8 T Cell Population Is Characterized by an Increased Frequency of Clonogenic Precursors

“…The fact that ex vivo unstimulated naive CD8 T cells from Rag Ϫ/Ϫ F5 mice are significantly larger than naive CD8 T cells from F5 mice favors this hypothesis (data not shown). Interestingly, increased clonogenicity of Rag Ϫ/Ϫ F5 naive CD8 T cell populations may explain why in some TCRtransgenic models no differences were found in the proliferative capacities of naive and primed populations (37). Indeed, in that case, all cells in the naive population may already be imprinted with clonogenic capacities.…”