Regulation of t cell effector function within the brain during acute viral encephalitis

D. Irani, D. Griffin

Research output: Contribution to journalArticle

Abstract

The unique stiudure and environment of the central nervous system (CNS) regulates the development and magnitude of mod local inflammatory responses. In some circumstances, however, this regulation fails and immune-mediated damage to the brain can occur. To bailer linderstand how lymphocyte function is regulated within the CNS during an immune response that does not produce local tissue injury, we have undertaken studies of T ceHs derived from the brains of mice with acute Sindbis virus (SV) encephalitis. These T eels faH to proliferate in vitro, either spontaneously or fofewing stimulation with mttogens and IL-2, despite expressing markers Indicative of activation. This lack of proliferation results from their apparent arrest in the cell cycle. In this setting, the expected phosphorylation of the ratinoMaetoma gene product (Rb), a critical cell cycle regulator, does not occur. Furthermore, while brain-derived T cells stimulated in HDD generate IFN-y, IL-4, and IL-10, they are unable to produce IL-2 at either the mRNA or the protein level. This pattern of cytokine production occurs in cells which are also deficient in their ability to activate the transcription factor NF-icB compared to lymphocytes isolated from extracerebral tissues. When T cells producing both IL-2 and IFN-y are adoptively transferred into SV-infected mice, some of these cells traffic into the brain. Those which enter the brain selectively down-regulate production of IL-2 over time. Collectively, these data show that the local environment of the CNS during SV encephalitis exerts a complex regulatory effect on T cells that are recruited into the brain. We speculate that this serves to prevent excessive local T ceH reactivity. Whether and how this regulation might faH in the setting of autoimmune neurologic disease remains to be explored.

Original languageEnglish (US)
Pages (from-to)A1274
JournalFASEB Journal
Volume10
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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