title: Enhancement of T cell responses as a result of synergy between lower doses of radiation and T cell stimulation.
abstract: As a side effect of cancer radiotherapy, immune cells receive varying doses of radiation. Whereas high doses of radiation (>10 Gy) can lead to lymphopenia, lower radiation doses (2-4 Gy) represent a valid treatment option in some hematological cancers, triggering clinically relevant immunological changes. Based on our earlier observations, we hypothesized that lower radiation doses have a direct positive effect on T cells. In this study, we show that 0.6-2.4 Gy radiation enhances proliferation and IFN-γ production of PBMC or purified T cells induced by stimulation via the TCR. Radiation with 1.2 Gy also lowered T cell activation threshold and broadened the Th1 cytokine profile. Although radiation alone did not activate T cells, when followed by TCR stimulation, ERK1/2 and Akt phosphorylation increased above that induced by stimulation alone. These changes were followed by an early increase in glucose uptake. Naive (CD45RA(+)) or memory (CD45RA(-)) T cell responses to stimulation were boosted at similar rates by radiation. Whereas increased Ag-specific cytotoxic activity of a CD8(+) T cell line manifested in a 4-h assay (10-20% increase), highly significant (5- to 10-fold) differences in cytokine production were detected in 6-d Ag-stimulation assays of PBMC, probably as a net outcome of death of nonstimulated and enhanced response of Ag-stimulated T cells. T cells from patients receiving pelvic radiation (2.2-2.75 Gy) also displayed increased cytokine production when stimulated in vitro. We report in this study enhanced T cell function induced by synergistic radiation treatment, with potential physiological significance in a wide range of T cell responses.
authors.affiliation: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Whitchurch, Cardiff CF14 2TL, United Kingdom.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Spary
authors.forename: Saly
authors.initials: S
authors.lastname: Al-Taei
authors.forename: Josephine
authors.initials: J
authors.lastname: Salimu
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Cook
authors.forename: Ann
authors.initials: A
authors.lastname: Ager
authors.forename: H Angharad
authors.initials: HA
authors.lastname: Watson
authors.forename: Aled
authors.initials: A
authors.lastname: Clayton
authors.forename: John
authors.initials: J
authors.lastname: Staffurth
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Mason
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Tabi
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000276:immunology / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D005947:Glucose / Q000276:immunology / Q000493:pharmacokinetics; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D008213:Lymphocyte Activation / Q000276:immunology / Q000528:radiation effects; D008297:Male; D010455:Peptides / Q000276:immunology*; D010766:Phosphorylation / Q000276:immunology / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000097:blood / Q000532:radiotherapy; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects*
chemical_list: D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D017493:Leukocyte Common Antigens; D005947:Glucose