Different T Cell Receptor Signals Determine CD8+ Memory Versus Effector Development (original) (raw)
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Frontiers in Immunology, 2013
Vaccines, arguably the single most important intervention in improving human health, have exploited the phenomenon of immunological memory. The elicitation of memory T cells is often an essential part of successful long-lived protective immunity. Our understanding of T cell memory has been greatly aided by the development of TCR Tg mice and MHC tetrameric staining reagents that have allowed the precise tracking of antigen-specific T cell responses. Indeed, following acute infection or immunization, naïve T cells undergo a massive expansion culminating in the generation of a robust effector T cell population. This peak effector response is relatively short-lived and, while most effector T cells die by apoptosis, some remain and develop into memory cells. Although the molecular mechanisms underlying this cell fate decision remain incompletely defined, substantial progress has been made, particularly with regards to CD8 + T cells. For example, the effector CD8 + T cells generated during a response are heterogeneous, consisting of cells with more or less potential to develop into full-fledged memory cells. Development of CD8 + T cell memory is regulated by the transcriptional programs that control the differentiation and survival of effector T cells. While the type of antigenic stimulation and level of inflammation control effector CD8 + T cell differentiation, availability of cytokines and their ability to control expression and function of Bcl-2 family members governs their survival. These distinct differentiation and survival programs may allow for finer therapeutic intervention to control both the quality and quantity of CD8 + T cell memory. Effector to memory transition of CD4 + T cells is less well characterized than CD8 + T cells, emerging details will be discussed. This review will focus on the recent progress made in our understanding of the mechanisms underlying the development of T cell memory with an emphasis on factors controlling survival of effector T cells.
The Impact of Pre-Existing Memory on Differentiation of Newly Recruited Naive CD8 T Cells
The Journal of Immunology, 2011
One goal of immunization is to generate memory CD8 T cells of sufficient quality and quantity to confer protection against infection. It has been shown that memory CD8 T cell differentiation in vivo is controlled, at least in part, by the amount and duration of infection, Ag, and inflammatory cytokines present early after the initiation of the response. In this study, we used models of anti-vectorial immunity to investigate the impact of pre-existing immunity on the development and differentiation of vector-induced primary CD8 T cell responses. We showed that existing CD8 T cell memory influences the magnitude of naive CD8 T cell responses. However, the differentiation of newly recruited (either TCR-transgenic or endogenous) primary CD8 T cells into populations with the phenotype (CD62Lhi, CD27hi, KLRG-1low) and function (tissue distribution, Ag-driven proliferation, cytokine production) of long-term memory was facilitated when they were primed in the presence of vector-specific mem...
The persistence of T cell memory
Cellular and Molecular Life Sciences, 2010
T cell memory is a crucial feature of the adaptive immune system in the defense against pathogens. During the last years, numerous studies have focused their efforts on uncovering the signals, inflammatory cues, and extracellular factors that support memory differentiation. This research is beginning to decipher the complex gene network that controls memory programming. However, how the different signals, that a T cell receives during the process of differentiation, interplay to trigger memory programming is still poorly defined. In this review, we focus on the most recent advances in the field and discuss how T cell receptor signaling and inflammation control CD8 memory differentiation.
Initial T cell frequency dictates memory CD8+ T cell lineage commitment
Nature Immunology, 2005
We show here that naive T cell precursor frequency profoundly influenced the pathway along which CD8 + memory T cells developed. At low precursor frequency, those T EM cells generated represented a stable cell lineage that failed to further differentiate into T CM cells. These findings do not adhere to the present dogma regarding memory T cell generation and provide a means for identifying factors controlling memory T cell lineage commitment.