Systemic depletion of lymphocytes following focal radiation to the brain in a murine model
Severe radiation-related lymphopenia is common and associated with decreased survival in patients with several solid tumors. As the mechanisms underlying systemic lymphopenia are poorly understood, we developed an animal model to study the effects of brain radiation on lymphocytes and cytokines. C57...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-07-01
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| Series: | OncoImmunology |
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| Online Access: | http://dx.doi.org/10.1080/2162402X.2018.1445951 |
| _version_ | 1811210125435731968 |
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| author | Anna F. Piotrowski Thomas R. Nirschl Esteban Velarde Lee Blosser Sudipto Ganguly Kathleen H. Burns Leo Luznik John Wong Charles G. Drake Stuart A. Grossman |
| author_facet | Anna F. Piotrowski Thomas R. Nirschl Esteban Velarde Lee Blosser Sudipto Ganguly Kathleen H. Burns Leo Luznik John Wong Charles G. Drake Stuart A. Grossman |
| author_sort | Anna F. Piotrowski |
| collection | DOAJ |
| description | Severe radiation-related lymphopenia is common and associated with decreased survival in patients with several solid tumors. As the mechanisms underlying systemic lymphopenia are poorly understood, we developed an animal model to study the effects of brain radiation on lymphocytes and cytokines. C57 BL/6 and BALB/c mice received focal brain irradiation (4 Gy x 10 fractions or 2 Gy x 30 fractions). Weekly total lymphocyte counts (TLC), lymphocyte subsets and cytokines in blood and lymph nodes were measured. Non-irradiated lymph nodes were collected and examined before, during, and after radiation. We found that systemic TLC decreased rapidly irrespective of mouse strain or radiation schedule. 4 Gy x 10 resulted in a 42% and 75% & 70% and 49% TLC reduction in C57 BL/6 and BALB/c mice respectively. 2 Gy x 30 caused a 70% / 49% decrease in TLC in C57 BL/6 and BALB/c. Similar trends were seen for total T cells, CD4+, regulatory T and CD8+ cells. Changes in lymph node architecture and cellular composition correlated with the development of systemic lymphopenia. Three weeks after radiation, TLC returned to 60–80% of baseline, preceded by increased IL-7 levels in the lymph nodes. Focal brain radiation in mice results in significant systemic lymphodepletion. |
| first_indexed | 2024-04-12T04:49:42Z |
| format | Article |
| id | doaj.art-f55f29d8c30e4f1182f3aaa6c0cac369 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-04-12T04:49:42Z |
| publishDate | 2018-07-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-f55f29d8c30e4f1182f3aaa6c0cac3692022-12-22T03:47:20ZengTaylor & Francis GroupOncoImmunology2162-402X2018-07-017710.1080/2162402X.2018.14459511445951Systemic depletion of lymphocytes following focal radiation to the brain in a murine modelAnna F. Piotrowski0Thomas R. Nirschl1Esteban Velarde2Lee Blosser3Sudipto Ganguly4Kathleen H. Burns5Leo Luznik6John Wong7Charles G. Drake8Stuart A. Grossman9Memorial Sloan Kettering Cancer CenterJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineJohns Hopkins University School of MedicineColumbia University Medical CenterJohns Hopkins University School of MedicineSevere radiation-related lymphopenia is common and associated with decreased survival in patients with several solid tumors. As the mechanisms underlying systemic lymphopenia are poorly understood, we developed an animal model to study the effects of brain radiation on lymphocytes and cytokines. C57 BL/6 and BALB/c mice received focal brain irradiation (4 Gy x 10 fractions or 2 Gy x 30 fractions). Weekly total lymphocyte counts (TLC), lymphocyte subsets and cytokines in blood and lymph nodes were measured. Non-irradiated lymph nodes were collected and examined before, during, and after radiation. We found that systemic TLC decreased rapidly irrespective of mouse strain or radiation schedule. 4 Gy x 10 resulted in a 42% and 75% & 70% and 49% TLC reduction in C57 BL/6 and BALB/c mice respectively. 2 Gy x 30 caused a 70% / 49% decrease in TLC in C57 BL/6 and BALB/c. Similar trends were seen for total T cells, CD4+, regulatory T and CD8+ cells. Changes in lymph node architecture and cellular composition correlated with the development of systemic lymphopenia. Three weeks after radiation, TLC returned to 60–80% of baseline, preceded by increased IL-7 levels in the lymph nodes. Focal brain radiation in mice results in significant systemic lymphodepletion.http://dx.doi.org/10.1080/2162402X.2018.1445951radiation-related lymphopenialymphocytesil-7 cytokinebrain radiationlymphodepletionimmunosuppression |
| spellingShingle | Anna F. Piotrowski Thomas R. Nirschl Esteban Velarde Lee Blosser Sudipto Ganguly Kathleen H. Burns Leo Luznik John Wong Charles G. Drake Stuart A. Grossman Systemic depletion of lymphocytes following focal radiation to the brain in a murine model OncoImmunology radiation-related lymphopenia lymphocytes il-7 cytokine brain radiation lymphodepletion immunosuppression |
| title | Systemic depletion of lymphocytes following focal radiation to the brain in a murine model |
| title_full | Systemic depletion of lymphocytes following focal radiation to the brain in a murine model |
| title_fullStr | Systemic depletion of lymphocytes following focal radiation to the brain in a murine model |
| title_full_unstemmed | Systemic depletion of lymphocytes following focal radiation to the brain in a murine model |
| title_short | Systemic depletion of lymphocytes following focal radiation to the brain in a murine model |
| title_sort | systemic depletion of lymphocytes following focal radiation to the brain in a murine model |
| topic | radiation-related lymphopenia lymphocytes il-7 cytokine brain radiation lymphodepletion immunosuppression |
| url | http://dx.doi.org/10.1080/2162402X.2018.1445951 |
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