Human bone marrow contains a subset of quiescent early memory CD8<sup>+</sup> T cells characterized by high CD127 expression and efflux capacity

Kudernatsch, Robert; Letsch, Anne; Guerreiro, Manuel; Löbel, Madlen; Bauer, Sandra; Volk, Hans‐Dieter; Scheibenbogen, Carmen

doi:10.1002/eji.201344180

Cited by 9 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This notion is supported by the different proliferation rates of CCR7-deficient and -sufficient CTL in mice that lack either IL-7 or IL-15, respectively [33]. Notably, T EM and T CM in human peripheral blood had a higher turnover as compared with the terminally differentiated T EMRA subset [42], and similar findings were reported for CD8 + T-cell subsets analyzed by Ki-67 staining in human BM [43]. Radbruch and colleagues reported that the fraction of Ki-67 + proliferating cells was significantly higher in CD4 + and CD8 + human memory T cells in peripheral blood, compared to the BM of the same individuals [44], and more prominent in cells that lacked IL-7Rα or CD69 expression.…”

supporting

confidence: 63%

Maintenance of memory CD8 T cells: Divided over division

2017

View full text Add to dashboard Cite

Once generated during an infection, memory CD8+ T cells can provide long-lasting protection against reinfection with an intracellular pathogen, but the longevity of this defense depends on the ability of these pathogen-specific memory cells to be maintained. Figure 1. Siracusa et al. [13] show that in the spleen, CD8 memory T cells are rapidly depleted upon CyP treatment, as they undergo homeostatic proliferation. In contrast, CD8 memory T cells in the BM are mostly quiescent, and thus protected from immediate depletion by CyP. These differences could be due to the supporting cell types that are present in spleen and bone marrow (e.g, more dendritic cells in the spleen), and/or differential expression of homeostatic cytokines.which are rapidly killed by CyP treatment (Fig. 1). Importantly, by treating mice with the drug FTY720, which inhibits egress of lymphocytes from lymphoid organs, the authors demonstrate that maintenance of memory CD8 T cells in the BM upon CyP treatment is not caused by a compensatory influx of peripheral CD8 T cells. A caveat of the study is that CyP also has some non-specific side-effects: CyP can deplete proliferating Tregs that in turn affect T cell homeostasis [15], and CyP has been shown to induce type 1 interferon and thereby increase proliferation of CD8 + memory T cells [16]. Nevertheless, the findings of Siracusa et al.[13] challenge our view on how memory CD8 T cells are maintained and suggest that the underlying mechanism may differ per organ. The conclusion that CD8 memory T cells in the BM are quiescent and do not proliferate, opposes previous studies from other groups regarding the maintenance of CD8 memory T cells in the BM. The group of Francesca di Rosa has published two papers showing that BM CD8 memory T cells contain a higher percentage of proliferating cells than their counterparts in either the spleen or lymph nodes, and this group proposed that the BM acts as a niche for antigen-independent proliferation of CD8 memory T cells [17,18]. Two other studies, of which one was in non-human primates, came to the same conclusion that homeostatic proliferation of memory CD8 T cells is most profound in the BM [12,19]. The discrepancies between the results of the Radbruch group and other groups regarding the proliferation of CD8 memory T cells in the BM remain unresolved, and could be due to many different factors. One key issue is the suspected induction of proliferation by BrdU treatment [10,18]. Most studies that have claimed higher proliferation of CD8 memory T cells in the BM as compared to the spleen, have done so based on BrdU incorporation by CD8 memory T cells [12,17,18]. In their 2015 study, Radbruch and colleagues showed that a 3 day treatment of 1 mg/mL BrdU in drinking water supplemented with sugar (which increases water consumption [20]) is sufficient to induce CD8 memory T-cell proliferation, with up to 75% of all CD8 memory T cells in the BM and spleen proliferating [10]. Of note, these percentages were much higher than those reported by the aforementioned stud...

show abstract

supporting

confidence: 63%

Maintenance of memory CD8 T cells: Divided over division

2017

View full text Add to dashboard Cite

show abstract

“…For example, a high proportion of BM memory CD4 and CD8 T cells express CD69 ( 22 , 23 , 32 ). Moreover, memory CD8 T cells from both mouse and human BM have a lower membrane expression of CD127, i.e., the IL-7Rα chain ( 8 , 22 , 59 , 61 ), with the exception of antigen-specific CD8 T cells from lymphocytic choriomeningitis virus (LCMV)-infected mice ( 23 ). The TNF-R family member GITR is selectively upregulated by a fraction of mouse BM memory CD8 T cells ( 56 ).…”

Section: Bone Marrow Memory T Cellsmentioning

confidence: 99%

Bone Marrow T Cells and the Integrated Functions of Recirculating and Tissue-Resident Memory T Cells

Rosa

Gebhardt

2016

Front. Immunol.

View full text Add to dashboard Cite

Changes in T cell trafficking accompany the naive to memory T cell antigen-driven differentiation, which remains an incompletely defined developmental step. Upon priming, each naive T cell encounters essential signals – i.e., antigen, co-stimuli and cytokines – in a secondary lymphoid organ; nevertheless, its daughter effector and memory T cells recirculate and receive further signals during their migration through various lymphoid and non-lymphoid organs. These additional signals from tissue microenvironments have an impact on immune response features, including T cell effector function, expansion and contraction, memory differentiation, long-term maintenance, and recruitment upon antigenic rechallenge into local and/or systemic responses. The critical role of T cell trafficking in providing efficient T cell memory has long been a focus of interest. It is now well recognized that naive and memory T cells have different migratory pathways, and that memory T cells are heterogeneous with respect to their trafficking. We and others have observed that, long time after priming, memory T cells are preferentially found in certain niches such as the bone marrow (BM) or at the skin/mucosal site of pathogen entry, even in the absence of residual antigen. The different underlying mechanisms and peculiarities of resulting immunity are currently under study. In this review, we summarize key findings on BM and tissue-resident memory (TRM) T cells and revisit some issues in memory T cell maintenance within such niches. Moreover, we discuss BM seeding by memory T cells in the context of migration patterns and protective functions of either recirculating or TRM T cells.

show abstract

“…Recent work suggests that MDR1 is expressed in the bone marrow by a quiescent population of early memory CD8 + T cells that proliferates efficiently in vitro in presence of viral peptides. 70 Turtle et al . also reported a memory CD8 + T cell subset (IL18Rα + CD161 + CD62L ± ) with high MDR1 expression endowed with stem cell properties and able to withstand high doses chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

MDR1 in immunity: friend or foe?

et al. 2018

View full text Add to dashboard Cite

MDR1 is an ATP-dependent transmembrane transporter primarily studied for its role in the detoxification of tissues and for its implication in resistance of tumor cells to chemotherapy treatment. Several studies also report on its expression on immune cells where it plays a protective role from xenobiotics and toxins. This review provides an overview of what is known on MDR1 expression in immune cells in human, and its implications in different pathologies and their treatment options.

show abstract

Human bone marrow contains a subset of quiescent early memory CD8⁺ T cells characterized by high CD127 expression and efflux capacity

Abstract: Even today it is still not completely understood how CD8+ T-cell memory is maintained long term.

Cited by 9 publications

References 36 publications

Maintenance of memory CD8 T cells: Divided over division

Maintenance of memory CD8 T cells: Divided over division

Bone Marrow T Cells and the Integrated Functions of Recirculating and Tissue-Resident Memory T Cells

MDR1 in immunity: friend or foe?

Contact Info

Product

Resources

About

Human bone marrow contains a subset of quiescent early memory CD8+ T cells characterized by high CD127 expression and efflux capacity

Abstract: Even today it is still not completely understood how CD8+ T-cell memory is maintained long term.

Cited by 9 publications

References 36 publications

Maintenance of memory CD8 T cells: Divided over division

Maintenance of memory CD8 T cells: Divided over division

Bone Marrow T Cells and the Integrated Functions of Recirculating and Tissue-Resident Memory T Cells

MDR1 in immunity: friend or foe?

Contact Info

Product

Resources

About

Human bone marrow contains a subset of quiescent early memory CD8⁺ T cells characterized by high CD127 expression and efflux capacity