Systemic depletion of lymphocytes following focal radiation to the brain in a murine model

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article numbere1445951
JournalOncoImmunology
Volume7
Issue number7
DOIs
StatePublished - Jul 3 2018

Keywords

  • IL-7 cytokine
  • brain radiation
  • immunosuppression
  • lymphocytes
  • lymphodepletion
  • radiation-related lymphopenia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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