Maintenance and Attrition of T-Cell Memory

Abstract

After antigenic stimulation in the context of "danger signals," naive T cells embark on a programmed, intense expansion phase to counteract the rapid proliferation of pathogens. During the first week of infection, responding T cells undergo > 1000-fold expansion, resulting in the development of large numbers of cells exhibiting potent effector function. As the pathogen (antigen) burden dwindles, a majority of the effectors generated are eliminated by apoptosis, resulting in the survival and maintenance of a small population of antigen-specific cells as long-term memory T cells. Depending on the infection studied, CD8+ T cells appear to differentiate through multiple pathways into resting and effector memory subsets, and require multiple cytokines and cell surface molecules for survival and proliferation. Once generated, the repertoire of memory T cells remains highly vulnerable to attrition during heterologous infections, where homeostatic forces drive deletions in T-cell memory pools to accommodate the entry of new memory T cells. This review will primarily focus on the factors that influence the generation, maintenance, and attrition of memory CD8+ T cells.

Nanoparticle conjugation of CpG enhances adjuvancy for cellular immunity and memory recall at low dose

“…One of the features expected by a prophylactic cellular immunity-inducing vaccine is induction of memory T cells that can be clonally expanded on recall (30). We first primed and boosted mice with our formulations to generate a pool of functional memory CTLs (14).…”

Peripheral “CD8 Tuning” Dynamically Modulates the Size and Responsiveness of an Antigen-Specific T Cell Pool In Vivo

“…After 48 h, the cells from each treatment were pooled, washed, and used as effector cells. EL4 cells were labeled with 51 Cr, then pulsed with 10 M of either HY or irrelevant (gp33) peptide and used as targets in a standard CTL assay (previously described in Ref. 24).…”

“…The substitutions of Smcy HY epitope were based on canonical MHC/TCR binding residues (31). These peptides were used to stimulate purified CD8 ϩ T cells from HY TCR female splenocytes in an in vitro proliferation assay (data not shown) and for a cytolytic assay where peptide stimulated cells were harvested and tested with EL4 cells pulsed with HY wild-type Smcy peptide in a standard 4-h 51 Cr release assay. Cells initially stimulated with C2A peptide gave a better CTL response than wild-type peptide, which was in turn better than K1A ( Fig.…”

Intracellular Bacterial Vectors That Induce CD8+ T Cells with Similar Cytolytic Abilities but Disparate Memory Phenotypes Provide Contrasting Tumor Protection

“…Moreover, cancer resurgence occurs despite the presence of tumor-specific CD8 + T cells (8). Memory CD8 + T cells are heterogeneous in phenotype: effectormemory (T EM ) and central-memory (T CM ) cells (9)(10)(11). Although both subtypes are antigen experienced, T EM have a decreased expression of CD62L that allows them to take up residence in peripheral nonlymphoid tissues, whereas T CM are CD62L high allowing them to localize to lymphatic tissues, and proliferate profoundly when reconfronted with antigen (9,(12)(13)(14).…”