title: Low-dose γ-rays modify CD4(+) T cell signalling response to simulated solar particle event protons in a mouse model.
abstract: OBJECTIVE
  Astronauts on missions are exposed to low-dose/low-dose-rate (LDR) radiation and could receive high doses during solar particle events (SPE). This study investigated T cell function in response to LDR radiation and simulated SPE (sSPE) protons, alone and in combination.
  
  
  METHODS
  C57BL/6 mice received LDR γ-radiation (⁵⁷Co) to a total dose of 0.01 Gray (Gy) at 0.179 mGy/h, either with or without subsequent exposure to 1.7 Gy sSPE protons delivered over 36 h. Mice were euthanised on days 4 and 21 post-exposure. T cells with cluster of differentiation 4 (CD4(+)) were negatively isolated from spleens and activated with anti-CD3 antibody. Cells and supernatants were evaluated for survival/signalling proteins and cytokines.
  
  
  RESULTS
  The most striking effects were noted on day 21. In the survival pathway, nuclear factor-kappaB (NF-κB; total and active forms) and p38 mitogen activated protein kinase (p38MAPK; total) were significantly increased and cJun N-terminal kinase (JNK; total and active) was decreased when mice were primed with LDR γ-rays prior to sSPE exposure (P < 0.001). Evaluation of the T cell antigen receptor (TCR) signalling pathway revealed that LDR γ-ray exposure normalised the high sSPE proton-induced level of lymphocyte specific protein tyrosine kinase (Lck; total and active) on day 21 (P < 0.001 for sSPE vs. LDR + sSPE), while radiation had no effect on active zeta-chain-associated protein kinase 70 (Zap-70). There was increased production of interleukin-2 (IL-2) and IL-4 and decreased transforming growth factor-β1 in the LDR + sSPE group compared to the sSPE group.
  
  
  CONCLUSIONS
  The data demonstrate, for the first time, that protracted exposure to LDR γ-rays can significantly modify the effects of sSPE protons on critical survival/signalling proteins and immunomodulatory cytokines produced by CD4(+) T cells.
authors.affiliation: Department of Radiation Medicine, Division of Biochemistry, Loma Linda University & Medical Center, Loma Linda, California, USA.
authors.forename: Asma
authors.initials: A
authors.lastname: Rizvi
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pecaut
authors.forename: James M
authors.initials: JM
authors.lastname: Slater
authors.forename: Shruti
authors.initials: S
authors.lastname: Subramaniam
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D002470:Cell Survival / Q000528:radiation effects; D016207:Cytokines / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays / Q000009:adverse effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008213:Lymphocyte Activation / Q000528:radiation effects; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D011522:Protons / Q000009:adverse effects; D015398:Signal Transduction / Q000528:radiation effects; D019445:Solar Activity; D018561:Space Simulation; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D011522:Protons; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases