title: Virus-induced transient immune suppression and the inhibition of T cell proliferation by type I interferon.
abstract: Vaccine-induced memory is necessary for protective immunity to pathogens, but many viruses induce a state of transient immune suppression that might contribute to the inability of a vaccine to elicit immunity. We evaluated here the fate of bystander T cells activated by third party cognate antigens during acute viral infections in vivo, using distinct models to track and specifically activate HY and P14 transgenic bystander CD8 T cells in vivo during acute arenavirus infections of mice. Viral infections acted as stimulatory adjuvants when bystander T cells were exposed to an inflammatory milieu and cognate antigens at the beginning of infections, but bystander CD8 T cell proliferation in response to cognate antigen was inhibited 3 to 9 days after virus infection. Reduced proliferation was not dependent on Fas-FasL- or tumor necrosis factor (TNF)-induced activation-induced cell death or on deficiencies of antigen presentation. Instead, reduced proliferation was associated with a delayed onset of division that was an intrinsic defect of T cells. Inhibition of proliferation could be simulated by exposure of T cells to the Toll-like receptor agonist and type I interferon (IFN) inducer poly(I · C). T cells lacking IFN-α/β receptors resisted both the suppressive effects of preexposure to poly(I · C) and the stimulatory effects of type I IFN, indicating that the timing of exposure to IFN can have negative or positive effects on T cell proliferation. Inhibition of T cell receptor-stimulated bystander CD8 T cell proliferation during acute viral infections may reflect the reduced ability of vaccines to elicit protective immunity when administered during an acute illness.
authors.affiliation: Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Heather D
authors.initials: HD
authors.lastname: Marshall
authors.forename: Stina L
authors.initials: SL
authors.lastname: Urban
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Welsh
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D005260:Female; D007165:Immunosuppression Therapy; D007370:Interferon Type I / Q000276:immunology* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018052:Pichinde virus / Q000276:immunology*
chemical_list: D007370:Interferon Type I