Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus
Cytomegalovirus (CMV) has been described as a contributor to immunosenescence, thus exacerbating age-related diseases. In persons with latent CMV infection, the CD8+ T cell compartment is irreversibly changed, leading to the accumulation of highly differentiated virus-specific CD8+ T cells in the pe...
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| Format: | Article |
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Frontiers Media S.A.
2017-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00715/full |
| _version_ | 1818914415041314816 |
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| author | Luca Pangrazzi Erin Naismith Andreas Meryk Michael Keller Brigitte Jenewein Klemens Trieb Beatrix Grubeck-Loebenstein |
| author_facet | Luca Pangrazzi Erin Naismith Andreas Meryk Michael Keller Brigitte Jenewein Klemens Trieb Beatrix Grubeck-Loebenstein |
| author_sort | Luca Pangrazzi |
| collection | DOAJ |
| description | Cytomegalovirus (CMV) has been described as a contributor to immunosenescence, thus exacerbating age-related diseases. In persons with latent CMV infection, the CD8+ T cell compartment is irreversibly changed, leading to the accumulation of highly differentiated virus-specific CD8+ T cells in the peripheral blood. The bone marrow (BM) has been shown to play a major role in the long-term survival of antigen-experienced T cells. Effector CD8+ T cells are preferentially maintained by the cytokine IL-15, the expression of which increases in old age. However, the impact of CMV on the phenotype of effector CD8+ T cells and on the production of T cell survival molecules in the BM is not yet known. We now show, using BM samples obtained from persons who underwent hip replacement surgery because of osteoarthrosis, that senescent CD8+ TEMRA cells with a bright expression of CD45RA and a high responsiveness to IL-15 accumulate in the BM of CMV-infected persons. A negative correlation was found between CMV antibody (Ab) titers in the serum and the expression of CD28 and IL-7Rα in CD8+TEMRAbright cells. Increased IL-15 mRNA levels were observed in the BM of CMV+ compared to CMV− persons, being particularly high in old seropositive individuals. In summary, our results indicate that a BM environment rich in IL-15 may play an important role in the maintenance of highly differentiated CD8+ T cells generated after CMV infection. |
| first_indexed | 2024-12-19T23:46:01Z |
| format | Article |
| id | doaj.art-c88071c21f574db396c1de8009334ad4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T23:46:01Z |
| publishDate | 2017-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c88071c21f574db396c1de8009334ad42022-12-21T20:01:18ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-06-01810.3389/fimmu.2017.00715273616Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with CytomegalovirusLuca Pangrazzi0Erin Naismith1Andreas Meryk2Michael Keller3Brigitte Jenewein4Klemens Trieb5Beatrix Grubeck-Loebenstein6Department of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, AustriaDepartment of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, AustriaDepartment of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, AustriaDepartment of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, AustriaDepartment of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, AustriaDepartment of Orthopedic Surgery, Hospital Wels-Grieskirchen, Wels, AustriaDepartment of Immunology, Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, AustriaCytomegalovirus (CMV) has been described as a contributor to immunosenescence, thus exacerbating age-related diseases. In persons with latent CMV infection, the CD8+ T cell compartment is irreversibly changed, leading to the accumulation of highly differentiated virus-specific CD8+ T cells in the peripheral blood. The bone marrow (BM) has been shown to play a major role in the long-term survival of antigen-experienced T cells. Effector CD8+ T cells are preferentially maintained by the cytokine IL-15, the expression of which increases in old age. However, the impact of CMV on the phenotype of effector CD8+ T cells and on the production of T cell survival molecules in the BM is not yet known. We now show, using BM samples obtained from persons who underwent hip replacement surgery because of osteoarthrosis, that senescent CD8+ TEMRA cells with a bright expression of CD45RA and a high responsiveness to IL-15 accumulate in the BM of CMV-infected persons. A negative correlation was found between CMV antibody (Ab) titers in the serum and the expression of CD28 and IL-7Rα in CD8+TEMRAbright cells. Increased IL-15 mRNA levels were observed in the BM of CMV+ compared to CMV− persons, being particularly high in old seropositive individuals. In summary, our results indicate that a BM environment rich in IL-15 may play an important role in the maintenance of highly differentiated CD8+ T cells generated after CMV infection.http://journal.frontiersin.org/article/10.3389/fimmu.2017.00715/fullbone marrowcytomegalovirusagingimmunosenescencesenescence |
| spellingShingle | Luca Pangrazzi Erin Naismith Andreas Meryk Michael Keller Brigitte Jenewein Klemens Trieb Beatrix Grubeck-Loebenstein Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus Frontiers in Immunology bone marrow cytomegalovirus aging immunosenescence senescence |
| title | Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus |
| title_full | Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus |
| title_fullStr | Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus |
| title_full_unstemmed | Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus |
| title_short | Increased IL-15 Production and Accumulation of Highly Differentiated CD8+ Effector/Memory T Cells in the Bone Marrow of Persons with Cytomegalovirus |
| title_sort | increased il 15 production and accumulation of highly differentiated cd8 effector memory t cells in the bone marrow of persons with cytomegalovirus |
| topic | bone marrow cytomegalovirus aging immunosenescence senescence |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.00715/full |
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