title: Effects of recombinant human granulocyte colony-stimulating factor on central and peripheral T lymphocyte reconstitution after sublethal irradiation in mice.
abstract: Granulocyte colony-stimulating factor (G-CSF) is one of the most critical cytokines used for the treatment of acute radiation syndrome (ARS). In addition to the hematopoietic effects of G-CSF on the differentiation and proliferation of myeloid progenitor cells, G-CSF is also known to have immunomodulatory effects. The aim of the present study was to investigate whether G-CSF could accelerate central and peripheral T lymphocyte recovery after a sublethal dose of irradiation. Female BALB/c mice were subjected to 6 Gy of total body irradiation and then were treated with either 100 μg/kg G-CSF or an equal volume of PBS once daily for 14 days. Percentages of thymocyte subpopulations including CD4 - CD8 - , CD4 + CD8 + , CD4 + CD8- and CD4 - CD8+ T cells, peripheral CD3 + , CD4+ and CD8+ cells were analyzed by flow cytometry. Recent thymic emigrants (RTEs) were assessed by real-time polymerase chain reaction (PCR) using primers specific to the 257-bp T cell receptor rearrangement excision circles (sjTRECs). The proliferative capacity of splenic mononuclear cells upon exposure to ConA was measured by using the Cell Count Kit-8 (CCK-8). G-CSF treatment promoted thymocyte regeneration, accelerated the recovery of CD4 + CD8+ cells and increased the frequency of thymocyte sjTRECs. These effects were more prominent at early time points (Day 28) after irradiation. G-CSF also increased the rate of recovery of peripheral CD3 + , CD4+ and CD8+ cells and shortened the period of severe lymphopenia following irradiation. G-CSF also increased the splenic mononuclear cell mitotic responsiveness to ConA more than control-treated cells. Our results show that G-CSF accelerates T cell recovery through both thymic-dependent and thymic-independent pathways, which could be used to increase the rate of immune reconstitution after sublethal irradiation.
authors.affiliation: Department of Hematology, Affiliated Hospital to the Academy of Military Medicine Science, 8th, East Street, FengTai District, Beijing, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhao
authors.forename: Mei
authors.initials: M
authors.lastname: Guo
authors.forename: Xuedong
authors.initials: X
authors.lastname: Sun
authors.forename: Wanjun
authors.initials: W
authors.lastname: Sun
authors.forename: Hailan
authors.initials: H
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Wei
authors.forename: Huisheng
authors.initials: H
authors.lastname: Ai
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D007928:Lethal Dose 50; D008231:Lymphopenia / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D013601:T-Lymphocytes / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D016896:Treatment Outcome; D014916:Whole-Body Irradiation / Q000009:adverse effects
chemical_list: D011837:Radiation-Protective Agents; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor