Cargando…

Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae

Bone marrow (BM) plays an important role in the long-term maintenance of memory T cells. Yet, BM is found in numerous bones throughout the body, which are not equal in structure, as they differ in their ratio of cortical and trabecular bone. This implies that BM cells within different bones are subj...

Descripción completa

Detalles Bibliográficos
Autores principales: Geerman, Sulima, Hickson, Sarah, Brasser, Giso, Pascutti, Maria Fernanda, Nolte, Martijn A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710685/
https://www.ncbi.nlm.nih.gov/pubmed/26793197
http://dx.doi.org/10.3389/fimmu.2015.00660
_version_ 1782409841047764992
author Geerman, Sulima
Hickson, Sarah
Brasser, Giso
Pascutti, Maria Fernanda
Nolte, Martijn A.
author_facet Geerman, Sulima
Hickson, Sarah
Brasser, Giso
Pascutti, Maria Fernanda
Nolte, Martijn A.
author_sort Geerman, Sulima
collection PubMed
description Bone marrow (BM) plays an important role in the long-term maintenance of memory T cells. Yet, BM is found in numerous bones throughout the body, which are not equal in structure, as they differ in their ratio of cortical and trabecular bone. This implies that BM cells within different bones are subjected to different microenvironments, possibly leading to differences in their frequencies and function. To address this, we examined BM from murine tibia, femur, pelvis, sternum, radius, humerus, calvarium, and the vertebrae and analyzed the presence of effector memory (T(EM)), central memory (T(CM)), and naïve (T(NV)) CD8(+) T cells. During steady-state conditions, the frequency of the total CD8(+) T cell population was comparable between all bones. Interestingly, most CD8(+) T cells were located in the vertebrae, as it contained the highest amount of BM cells. Furthermore, the frequencies of T(EM), T(CM), and T(NV) cells were similar between all bones, with a majority of T(NV) cells. Additionally, CD8(+) T cells collected from different bones similarly expressed the key survival receptors IL-7Rα and IL-15Rβ. We also examined BM for memory CD8(+) T cells with a tissue-resident memory phenotype and observed that approximately half of all T(EM) cells expressed the retention marker CD69. Remarkably, in the memory phase of acute infection with the lymphocytic choriomeningitis virus (LCMV), we found a massive compositional change in the BM CD8(+) T cell population, as the T(EM) cells became the dominant subset at the cost of T(NV) cells. Analysis of Ki-67 expression established that these T(EM) cells were in a quiescent state. Finally, we detected higher frequencies of LCMV-specific CD8(+) T cells in BM compared to spleen and found that BM in its entirety contained fivefold more LCMV-specific CD8(+) T cells. In conclusion, although infection with LCMV caused a dramatic change in the BM CD8(+) T cell population, this did not result in noticeable differences between BM collected from different bones. Our findings suggest that in respect to CD8(+) T cells, BM harvested from a single bone is a fair reflection of the rest of the BM present in the murine body.
format Online
Article
Text
id pubmed-4710685
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-47106852016-01-20 Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae Geerman, Sulima Hickson, Sarah Brasser, Giso Pascutti, Maria Fernanda Nolte, Martijn A. Front Immunol Immunology Bone marrow (BM) plays an important role in the long-term maintenance of memory T cells. Yet, BM is found in numerous bones throughout the body, which are not equal in structure, as they differ in their ratio of cortical and trabecular bone. This implies that BM cells within different bones are subjected to different microenvironments, possibly leading to differences in their frequencies and function. To address this, we examined BM from murine tibia, femur, pelvis, sternum, radius, humerus, calvarium, and the vertebrae and analyzed the presence of effector memory (T(EM)), central memory (T(CM)), and naïve (T(NV)) CD8(+) T cells. During steady-state conditions, the frequency of the total CD8(+) T cell population was comparable between all bones. Interestingly, most CD8(+) T cells were located in the vertebrae, as it contained the highest amount of BM cells. Furthermore, the frequencies of T(EM), T(CM), and T(NV) cells were similar between all bones, with a majority of T(NV) cells. Additionally, CD8(+) T cells collected from different bones similarly expressed the key survival receptors IL-7Rα and IL-15Rβ. We also examined BM for memory CD8(+) T cells with a tissue-resident memory phenotype and observed that approximately half of all T(EM) cells expressed the retention marker CD69. Remarkably, in the memory phase of acute infection with the lymphocytic choriomeningitis virus (LCMV), we found a massive compositional change in the BM CD8(+) T cell population, as the T(EM) cells became the dominant subset at the cost of T(NV) cells. Analysis of Ki-67 expression established that these T(EM) cells were in a quiescent state. Finally, we detected higher frequencies of LCMV-specific CD8(+) T cells in BM compared to spleen and found that BM in its entirety contained fivefold more LCMV-specific CD8(+) T cells. In conclusion, although infection with LCMV caused a dramatic change in the BM CD8(+) T cell population, this did not result in noticeable differences between BM collected from different bones. Our findings suggest that in respect to CD8(+) T cells, BM harvested from a single bone is a fair reflection of the rest of the BM present in the murine body. Frontiers Media S.A. 2016-01-13 /pmc/articles/PMC4710685/ /pubmed/26793197 http://dx.doi.org/10.3389/fimmu.2015.00660 Text en Copyright © 2016 Geerman, Hickson, Brasser, Pascutti and Nolte. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Geerman, Sulima
Hickson, Sarah
Brasser, Giso
Pascutti, Maria Fernanda
Nolte, Martijn A.
Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae
title Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae
title_full Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae
title_fullStr Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae
title_full_unstemmed Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae
title_short Quantitative and Qualitative Analysis of Bone Marrow CD8(+) T Cells from Different Bones Uncovers a Major Contribution of the Bone Marrow in the Vertebrae
title_sort quantitative and qualitative analysis of bone marrow cd8(+) t cells from different bones uncovers a major contribution of the bone marrow in the vertebrae
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4710685/
https://www.ncbi.nlm.nih.gov/pubmed/26793197
http://dx.doi.org/10.3389/fimmu.2015.00660
work_keys_str_mv AT geermansulima quantitativeandqualitativeanalysisofbonemarrowcd8tcellsfromdifferentbonesuncoversamajorcontributionofthebonemarrowinthevertebrae
AT hicksonsarah quantitativeandqualitativeanalysisofbonemarrowcd8tcellsfromdifferentbonesuncoversamajorcontributionofthebonemarrowinthevertebrae
AT brassergiso quantitativeandqualitativeanalysisofbonemarrowcd8tcellsfromdifferentbonesuncoversamajorcontributionofthebonemarrowinthevertebrae
AT pascuttimariafernanda quantitativeandqualitativeanalysisofbonemarrowcd8tcellsfromdifferentbonesuncoversamajorcontributionofthebonemarrowinthevertebrae
AT noltemartijna quantitativeandqualitativeanalysisofbonemarrowcd8tcellsfromdifferentbonesuncoversamajorcontributionofthebonemarrowinthevertebrae