Regulatory T Cells in [gamma] 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: Public Library of Science 19-06-2012
• Subjects: Antigens; Apoptosis; Ionizing radiation; Radiation victims; Skin; T cells; Vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0039092

Sublethal total body [gamma] 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.