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Review
. 2010 Jul:236:151-66.
doi: 10.1111/j.1600-065X.2010.00926.x.

Generation of effector CD8+ T cells and their conversion to memory T cells

Weiguo Cui  1 , Susan M Kaech
Affiliations
Review

Generation of effector CD8+ T cells and their conversion to memory T cells

Weiguo Cui et al. Immunol Rev. 2010 Jul.

Abstract

Immunological memory is a cardinal feature of adaptive immunity. We are now beginning to elucidate the mechanisms that govern the formation of memory T cells and their ability to acquire longevity, survive the effector-to-memory transition, and mature into multipotent, functional memory T cells that self-renew. Here, we discuss the recent findings in this area and highlight extrinsic and intrinsic factors that regulate the cellular fate of activated CD8+ T cells.

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Figures

Fig. 1
Fig. 1. Generation of effector CD8+ T cells and progressive differentiation into memory T cells
In response to infections, naive CD8+ T cells become activated, proliferate rapidly, and differentiate into a heterogeneous pool of effector CD8+ T cells. Most cells terminally differentiate into end-stage effectors that have a shortened lifespan and die following infection, whereas a smaller subset of cells differentiates into memory cell precursors that can further mature into functional memory cells that self-renew. Exposure to high levels of proinflammatory cytokines, such as IL-12, IFN-γ, and IL-2, causes upregulation of T-bet and Bilmp-1 as well as increased mTOR activity in activated CD8+ T cells, which in turn promotes effector cells to terminally differentiate and die via Bim-dependent apoptosis. By contrast, a group of cells upregulate BCL-6, Bmi-1, Tcf7, and possibly Eomes when they either circumvent high levels of proinflammatory cytokines or possibly encounter pro-memory signals. They can also switch from mTOR-mediated anabolic state to AMPK/FAO-mediated catabolic state following growth factor withdrawal and survive effector-to-memory transition by upregulating anti-apoptosis factors, such as Bcl-2 and Mcl-1. Between these two cell subsets (SLEC in dark purple and MPEC in orange), additional types of effector CD8+ T cells exist that appear to display a mix of terminally differentiated and memory precursor cell properties and have intermediate lifespans and proliferative potential. After pathogen clearance, effector CD8+ T cells give rise to diverse subsets of memory T cells, including end-stage TEM, TTM, TEM, and TCM. End-stage TEM cells are more effector like, have poor recall ability, and gradually decay from the memory pool. TTM continually differentiate into TCM that persist for a long term via homeostatic turn over, acquire homing ability to SLOs, produce IL-2, and mount robust secondary response upon recall. TEM cells usually reside in periphery tissues and retain their cytolytic activity, thereby providing immediate effector function at the portal of pathogen entry, but exhibiting reduced proliferative capacity. IL, interleukin; IFN-γ, interferon-γ; mTOR, mammalian target of rapamycin; AMPK, 5′-adenosine monophosphate-activated protein kinase; FAO, fatty acid oxidation; SLEC, short-lived effector cell; MPEC, memory precursor effector cell; TEM, effector memory T cells; TTM, transitional TEM; TCM, ‘central’ memory CD8+ T cells; SLO, secondary lymphoid organ.
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