PD-1 IS HIGHLY EXPRESSED ON MEMORY T-CELL SUBSETS RESIDING IN BONE MARROW BUT NOT IN PE-RIPHERAL BLOOD IN HEALTHY INDIVIDUALS.
(Abstract release date: 05/18/17)
EHA Library. Popova N. 05/18/17; 182566; PB1852
Natalia Popova
Contributions
Contributions
Abstract
Abstract: PB1852
Type: Publication Only
Background
Recently memory T lymphocytes were shown to be a highly heterogeneous cell compartment comprising different phenotypes, functional activities, gene expression profiles and survival capacities. Phenotypically due to the differentiation stage and functional activities memory CD8+ T cells can be divided into stem cell memory (Tscm), central memory (Tcm), terminal memory (Ttm), effector memory (Tem) and terminal effector (Tte) and reside in bone marrow (BM) as long-lived persistent T cells [Mahnke YD et al., 2013]. Programmed cell death protein 1 (PD-1) is well known as a negative immune regulator of T cells that has detrimental effects on anti-viral, anti-tumor immunity, mediates tissue tolerance to protect against immune-mediated tissue damage. Currently anti-PD1 immunotherapies are among the most effective anti-cancer immunotherapies available. PD1 pathway blockade is a key pathogenetic mechanism [Boussiotis VA et al., 2014]. Understanding the influence of PD-1 pathway on memory T cell homeostasis in BM might be critical for improving treatment of patients with cancers and hematological malignancies, but is still not well understood.
Aims
To evaluate PD-1 expression on distinct memory T cell subsets in BM and PB of healthy donors.
Methods
The first portion of BM and a sample of PB were obtained from healthy donors (n=10, m=6, f=4) with age 37.5 (22-53) years old.. Numbers of white blood cells (WBC) in BM and PB samples were evaluated by Sysmex XE-2100 hematology analyzer. 1*10^6 of WBC (excluded nucleated red blood cell) from BM and PB were stained using “lyse-wash-stain” standard protocol. The CD8-APC-Cy7, CCR7-PE-Cy7, CD28-PE, CD45R0-FITS, PD1-APC antibodies were used for cell staining and 7-AAD was used for to discriminate dead cells during flow cytometry.
Results
PD1 expression by T memory cell subsets is shown in the Table 1 (median with interquartile range). The percentage of PD1+ cells within Tcm CD8+ subset was 34,2%±8,033% in BM versus 10,4%±1,23% in PB. Similar trend was observed in other subsets: Tscm, Tem, Ttm, Tte. Median of PD1+ CD8+ cells were 3,8%±1,015%, 22,7%±6,39%, 42,7%±7,86%, 21,9%±4,047% and 2,6%±0,41%, 6,6%±2,59%, 12,7%±1,25%, 8,9%±0,825% in BM and in PB respectively.
PD1 expression (median with IQR) | Tnv+Tscm CD45R0+ CCR7+CD28+ | Tcm CD45R0-CCR7+CD28+ | Ttm CD45R0-CCR7-CD28+ | Tem CD45R0-CCR7-CD28- | Tte CD45R0+CCR7-CD28- |
BM | 3,8 %±1,015% ns | 34,2%±8,033% p<0,01 | 42,7%±7,86% p<0,01 | 22,7%±6,39% p<0,01 | 21,9%±4,047% p<0,01 |
PB | 2,6 %±0,41% | 10,4%±1,23% | 12,7%±1,25% | 6,6%±2,59% | 8,9%±0,825% |
Conclusion
We found higher frequencies of PD-1 expressing memory ВМ T cells comparing to PB. This might point to the important roles of PD-1 in regulation of memory T cells homeostasis in BM. In physiological conditions PD-1 is thought to neutralize self-reactive naive T cells that in its turn leads to restraining T cells excessive activation and blockade the development of autoimmunity in BM. On the other hand low expression of PD1 on T cells in PB can be explained by needs the opportunity for prompt reactivity with pathogens that also provide normal «robust control» and prevent developing of a disease.
Session topic: 23. Hematopoiesis, stem cells and microenvironment
Keyword(s): Memory T cells, Immunology, Hematopoiesis
Abstract: PB1852
Type: Publication Only
Background
Recently memory T lymphocytes were shown to be a highly heterogeneous cell compartment comprising different phenotypes, functional activities, gene expression profiles and survival capacities. Phenotypically due to the differentiation stage and functional activities memory CD8+ T cells can be divided into stem cell memory (Tscm), central memory (Tcm), terminal memory (Ttm), effector memory (Tem) and terminal effector (Tte) and reside in bone marrow (BM) as long-lived persistent T cells [Mahnke YD et al., 2013]. Programmed cell death protein 1 (PD-1) is well known as a negative immune regulator of T cells that has detrimental effects on anti-viral, anti-tumor immunity, mediates tissue tolerance to protect against immune-mediated tissue damage. Currently anti-PD1 immunotherapies are among the most effective anti-cancer immunotherapies available. PD1 pathway blockade is a key pathogenetic mechanism [Boussiotis VA et al., 2014]. Understanding the influence of PD-1 pathway on memory T cell homeostasis in BM might be critical for improving treatment of patients with cancers and hematological malignancies, but is still not well understood.
Aims
To evaluate PD-1 expression on distinct memory T cell subsets in BM and PB of healthy donors.
Methods
The first portion of BM and a sample of PB were obtained from healthy donors (n=10, m=6, f=4) with age 37.5 (22-53) years old.. Numbers of white blood cells (WBC) in BM and PB samples were evaluated by Sysmex XE-2100 hematology analyzer. 1*10^6 of WBC (excluded nucleated red blood cell) from BM and PB were stained using “lyse-wash-stain” standard protocol. The CD8-APC-Cy7, CCR7-PE-Cy7, CD28-PE, CD45R0-FITS, PD1-APC antibodies were used for cell staining and 7-AAD was used for to discriminate dead cells during flow cytometry.
Results
PD1 expression by T memory cell subsets is shown in the Table 1 (median with interquartile range). The percentage of PD1+ cells within Tcm CD8+ subset was 34,2%±8,033% in BM versus 10,4%±1,23% in PB. Similar trend was observed in other subsets: Tscm, Tem, Ttm, Tte. Median of PD1+ CD8+ cells were 3,8%±1,015%, 22,7%±6,39%, 42,7%±7,86%, 21,9%±4,047% and 2,6%±0,41%, 6,6%±2,59%, 12,7%±1,25%, 8,9%±0,825% in BM and in PB respectively.
PD1 expression (median with IQR) | Tnv+Tscm CD45R0+ CCR7+CD28+ | Tcm CD45R0-CCR7+CD28+ | Ttm CD45R0-CCR7-CD28+ | Tem CD45R0-CCR7-CD28- | Tte CD45R0+CCR7-CD28- |
BM | 3,8 %±1,015% ns | 34,2%±8,033% p<0,01 | 42,7%±7,86% p<0,01 | 22,7%±6,39% p<0,01 | 21,9%±4,047% p<0,01 |
PB | 2,6 %±0,41% | 10,4%±1,23% | 12,7%±1,25% | 6,6%±2,59% | 8,9%±0,825% |
Conclusion
We found higher frequencies of PD-1 expressing memory ВМ T cells comparing to PB. This might point to the important roles of PD-1 in regulation of memory T cells homeostasis in BM. In physiological conditions PD-1 is thought to neutralize self-reactive naive T cells that in its turn leads to restraining T cells excessive activation and blockade the development of autoimmunity in BM. On the other hand low expression of PD1 on T cells in PB can be explained by needs the opportunity for prompt reactivity with pathogens that also provide normal «robust control» and prevent developing of a disease.
Session topic: 23. Hematopoiesis, stem cells and microenvironment
Keyword(s): Memory T cells, Immunology, Hematopoiesis
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