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. 2016 Sep 1;12(9):e1005722.
doi: 10.1371/journal.ppat.1005722. eCollection 2016 Sep.

Memory CD8+ T Cells: Orchestrators and Key Players of Innate Immunity?

Grégoire Lauvau  1 , Stanislas Goriely  2
Affiliations

Memory CD8+ T Cells: Orchestrators and Key Players of Innate Immunity?

Grégoire Lauvau et al. PLoS Pathog. .

Abstract

Over the past decades, the dichotomy between innate and adaptive immune responses has largely dominated our understanding of immunology. Upon primary encounter with microbial pathogens, differentiation of adaptive immune cells into functional effectors usually takes several days or even longer, making them contribute to host protection only late during primary infection. However, once generated, antigen-experienced T lymphocytes can persist in the organism and constitute a pool of memory cells that mediate fast and effective protection to a recall infection with the same microbial pathogen. Herein, we challenge this classical paradigm by highlighting the "innate nature" of memory CD8+ T cells. First, within the thymus or in the periphery, naïve CD8+ T cells may acquire phenotypic and functional characteristics of memory CD8+ T cells independently of challenge with foreign antigens. Second, both the "unconventional" and the "conventional" memory cells can rapidly express protective effector functions in response to sets of inflammatory cytokines and chemokines signals, independent of cognate antigen triggering. Third, memory CD8+ T cells can act by orchestrating the recruitment, activation, and licensing of innate cells, leading to broad antimicrobial states. Thus, collectively, memory CD8+ T cells may represent important actors of innate immune defenses.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Pathway of conventional and unconventional CD8 T cell memory differentiation.
Naïve CD8 T cells undergoing cognate antigen recognition in the context of an infection or an immunization differentiate into effector cells and form “true” antigen-experienced memory cells or "conventional memory." Under physiological conditions, naïve CD8 T cells may also acquire a memory phenotype in the absence of non-self cognate antigenic stimulation. This may occur in the thymus or in the periphery under the control of cytokines such as IL-4, IL-15, and type I IFN and give rise to “virtual memory” or "innate/memory-like" CD8 T cells.
Fig 2
Fig 2. Mechanisms of memory CD8 T reactivation and orchestration of protective immune responses.
Upon contact with microbial pathogen, different myeloid subpopulations may rapidly activate memory CD8 T cells through cytokinic and antigenic signals (Phase 1). In turn, memory CD8 T cells produce various cytokines and chemokines (IFNγ, CCL3) that allow initial recruitment and licencing of innate immune cells (Phase 2). Myeloid cells further amplify recruitment (CXCL9/10) of more memory T and innate effectors cells leading to pathogen containement and protective immunity (Phase 3).
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