Regulatory T cells in γ irradiation-induced immune suppression

• Published in: PloS one Vol. 7; no. 6; p. e39092
• Main Authors: McFarland, Hugh I, Puig, Montserrat, Grajkowska, Lucja T, Tsuji, Kazuhide, Lee, Jay P, Mason, Karen P, Verthelyi, Daniela, Rosenberg, Amy S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.06.2012; Public Library of Science (PLoS)
• Subjects: Animals; Antigens; Apoptosis; Asthma; Biology; CD25 antigen; CD4 antigen; CD8 antigen; CD8 Antigens - genetics; CD8-Positive T-Lymphocytes - immunology; Cell Cycle - radiation effects; Cytokines; Effector cells; Epitopes - immunology; Exposure; Food; Forkhead Transcription Factors - genetics; Foxp3 protein; Gamma irradiation; Gamma Rays - adverse effects; Gene expression; Graft rejection; Graft Rejection - immunology; Graft Rejection - prevention & control; Graft Survival - genetics; Graft Survival - immunology; Grafting; Histocompatibility Antigens Class I - immunology; Homeostasis; Immunity; Immunologic Memory; Immunological memory; Immunoregulation; Immunosuppression; Ionizing radiation; Irradiation; Kinetics; Lymphocyte Depletion; Lymphocytes; Lymphocytes T; Major histocompatibility complex; Medical imaging; Mice; Mice, Transgenic; Plastic surgery; Proteins; Radiation; Radiation effects; Rejection; Skin; Skin & tissue grafts; Skin grafts; Skin Transplantation - immunology; Stem cells; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - radiation effects; Transcription, Genetic; Transplantation, Homologous - immunology; Whole-Body Irradiation; X-rays; United States > US; Maryland
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0039092

Sublethal total body γ irradiation (TBI) of mammals causes generalized immunosuppression, in part by induction of lymphocyte apoptosis. Here, we provide evidence that a part of this immune suppression may be attributable to dysfunction of immune regulation. We investigated the effects of sublethal TBI on T cell memory responses to gain insight into the potential for loss of vaccine immunity following such exposure. We show that in mice primed to an MHC class I alloantigen, the accelerated graft rejection T memory response is specifically lost several weeks following TBI, whereas identically treated naïve mice at the same time point had completely recovered normal rejection kinetics. Depletion in vivo with anti-CD4 or anti-CD25 showed that the mechanism involved cells consistent with a regulatory T cell (T reg) phenotype. The loss of the T memory response following TBI was associated with a relative increase of CD4+CD25+ Foxp3+ expressing T regs, as compared to the CD8+ T effector cells requisite for skin graft rejection. The radiation-induced T memory suppression was shown to be antigen-specific in that a third party ipsilateral graft rejected with normal kinetics. Remarkably, following the eventual rejection of the first MHC class I disparate skin graft, the suppressive environment was maintained, with markedly prolonged survival of a second identical allograft. These findings have potential importance as regards the immunologic status of T memory responses in victims of ionizing radiation exposure and apoptosis-inducing therapies.