Defining Memory CD8 T Cell

Abstract

CD8 T cells comprising the memory pool display considerable heterogeneity, with individual cells differing in phenotype and function. This review will focus on our current understanding of heterogeneity within the antigen-specific memory CD8 T cell compartment and classifications of memory CD8 T cell subsets with defined and discrete functionalities. Recent data suggest that phenotype and/or function of numerically stable circulatory memory CD8 T cells are defined by the age of memory CD8 T cell (or time after initial antigen-encounter). In addition, history of antigen stimulations has a profound effect on memory CD8 T cell populations, suggesting that repeated infections (or vaccination) have the capacity to further shape the memory CD8 T cell pool. Finally, genetic background of hosts and history of exposure to diverse microorganisms likely contribute to the observed heterogeneity in the memory CD8 T cell compartment. Extending our tool box and exploring alternative mouse models (i.e., “dirty” and/or outbred mice) to encompass and better model diversity observed in humans will remain an important goal for the near future that will likely shed new light into the mechanisms that govern biology of memory CD8 T cells.

Liposomes used as a vaccine adjuvant-delivery system: From basics to clinical immunization

“…One downstream contributes to the cellular responses, whereby, the APC MHC-I-Ag epitopes bind to TCRs of CD8+ T cells, which, under additional co-stimulation of, usually, IL-12 and IFN-γ secreted mainly by activated Th1 cells, will turn into via differentiation the Ag-specific CTLs (cytotoxic T lymphocytes) and memory CTLs (MCTLs) ( Fig. 1) [38]. Both CTLs may migrate to circulation system and peripheral tissues and are able to recognize and bind via TCRs to the identical MHC-I-Ag epitopes presented on the encountered pathogen-hidden or diseased cells.…”

“…Generally, the T-dependent process is able to imprint immune system with Ag features to establish the immune memory, which is marked by forming the long-lived memory T cells (including CD4+ and CD8+ MTCs) [38,43], possibly, derived from their effector counterparts [44], and long-lived memory B cells in LNs, spleen and peripheral tissues [45]. The generated immune memory is thought the most important consequence of vaccination as it enables the pathogen-experienced hosts to possess the ability of rapidly initiating responses to the encountered pathogens bearing identical Ags, thus engendering prompt immunity to remove invaders [32].…”

Delineation of a molecularly distinct terminally differentiated memory CD8 T cell population

“…Rictor, T-bet, and Zeb2 were among the top predicted candidates promoting the terminal-TEM fate; all three factors have previously established roles in supporting TE formation (11,17,18,55). T-bet is also widely considered to be essential for conventional TEM formation (3,56); however, the computational approach predicted T-bet to be more influential in supporting terminal-TEM compared to both TEM and TCM. To evaluate the fate-specifying role of T-bet on TEM and terminal-TEM differentiation, we co-transferred Tbx21 +/+ or Tbx21 +/-OT-I cells at 1:1 ratio into congenically distinct recipient mice subsequently infected with LCMV-OVA ( Fig.…”

Innate and secondary humoral responses are improved by increasing the time between MVA vaccine immunizations

“…In any case, these results clearly demonstrate a greater innate effector response to revaccination at 2 months than to vaccination or to revaccination at 2 weeks. However, this type of functional analysis cannot fully resolve whether the increased cytokine response corresponded to the enhanced intrinsic responsiveness of innate cells to MVA re-encounter (reminiscent of innate immune training), and/or to their enhanced activation and licensing by immune complexes and restimulated primary T cells 26 , of which their functions depend on time after initial antigen exposure 27 . Nonetheless, as previously shown, IL-12 expression was augmented in monocytes and cDCs induced by prime, present prior to a second immunization at 2 months, responding to it, and characteristic of it based on the LDA classification 15 .…”