Defining the molecular blueprint that drives CD8+ T cell differentiation in response to infection

Brendan E Russ,Alice E Denton,Stephen J Turner,Matthew R Olson,Lauren Hatton,Hayley Croom

doi:10.3389/fimmu.2012.00371

Brendan E Russ, Alice E Denton + Show 4 more

Open Access

https://doi.org/10.3389/fimmu.2012.00371

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Journal: Frontiers in Immunologie	Publication Date: Jan 1, 2012
Citations: 59	License type: cc-by

Affiliation: University of Melbourne

Abstract

A cardinal feature of adaptive, cytotoxic T lymphocyte (CTL)-mediated immunity is the ability of naïve CTLs to undergo a program of differentiation and proliferation upon activation resulting in the acquisition of lineage-specific T cell functions and eventual establishment of immunological memory. In this review, we examine the molecular factors that shape both the acquisition and maintenance of lineage-specific effector function in virus-specific CTL during both the effector and memory phases of immunity.

Highlights

A cardinal feature of adaptive, cytotoxic T lymphocyte (CTL)mediated immunity is the ability of naïve CTLs to undergo a program of differentiation and proliferation upon activation resulting in the acquisition of lineage-specific T cell functions and eventual establishment of immunological memory (Kaech et al, 2002a; van Stipdonk et al, 2003)
CTLs contribute to the control and eventual elimination of a myriad of pathogen and tumor challenges via the coordinated interplay of varied effector mechanisms that include; (1) the production of pro-inflammatory cytokines such as interferon (IFN)-γ and tumor necrosis factor (TNF)-α (La Gruta et al, 2004); and (2) the expression of cytolytic effector molecules including perforin (Pfp; Kagi et al, 1994) and the granule enzymes A, B, and K (Jenkins et al, 2007; Peixoto et al, 2007; Moffat et al, 2009)
Our understanding of the factors that shape the cell fate decisions to be a memory versus effector T cells are unclear, but the molecular mechanisms that enable stable maintenance of rapid effector function in the long-term are not well understood

Summary

Introduction

A cardinal feature of adaptive, cytotoxic T lymphocyte (CTL)mediated immunity is the ability of naïve CTLs to undergo a program of differentiation and proliferation upon activation resulting in the acquisition of lineage-specific T cell functions and eventual establishment of immunological memory (Kaech et al, 2002a; van Stipdonk et al, 2003). Expression of the transcription factor Foxo1 actively represses effector differentiation by blocking T-bet expression, while at the same time promoting Eomes expression and maintenance of memory T cell generation (Rao et al, 2012).

Results

Conclusion