Transcription of signal-3 cytokines, IL-12 and IFNalphaß, coincides with the timing of CD8alphaß up-regulation durinig viral infection of common carp (Cyprinus carpio L.)

M. Forlenza, J.D.A. de Carvalho Dias, E.T. Vesely, D. Pokorova, H.F.J. Savelkoul, G.F. Wiegertjes

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60 Citations (Scopus)

Abstract

Mammalian naïve CD8+ T cells are activated by antigen (signal 1) and CD28 costimulation (signal 2) to undergo several rounds of cell division, but programming for survival, effector function and memory requires a third signal that can be provided by IL-12 and/or type I interferons. Functional studies indicate that the route of antigen presentation and costimulation are conserved from fish to mammals. However, the potential of IL-12 and IFN¿ß to act as signal-3 cytokines in infections inducing a CTL response has not been examined in fish. We report the cloning of CD8¿ and CD8ß homologues, each present in duplicate copies and of two TCR-C¿ isoforms in European common carp. The identification of (cytotoxic) T cell marker sequences and the availability of sequences coding for the signal-3 cytokines in the same fish species, allowed us to investigate by RT-qPCR their kinetics of gene expression during viral and parasitic infection. Our results show that transcription of signal-3 cytokines occurred concomitantly with CD8¿ß up-regulation exclusively at 4 days post-primary viral infection. No regulation of IL-12 and IFN¿ß was observed after parasitic infection. Our data provide evidences for an evolutionary conservation of function for IL-12 and IFN¿ß to act as third signal during CTL activation. In addition, we suggest that a CD8¿2/ß1 and a p35p40b association could be the preferred combinations for the formation of a functional CD8 co-receptor and an IL-12p70 heterodimer during viral infection. The relevance of our findings to future vaccination strategies in fish is discussed.
Original languageEnglish
Pages (from-to)1531-1547
JournalMolecular Immunology
Volume45
Issue number6
DOIs
Publication statusPublished - 2008

Keywords

  • cell-mediated cytotoxicity
  • ginbuna crucian carp
  • cd8 t-cells
  • dicentrarchus-labrax l.
  • clonal expansion
  • teleost fish
  • coreceptor function
  • effector function
  • rainbow-trout
  • genetic-variability

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