Regulation of Brain-Derived T Cells during Acute Central Nervous System Inflammation

David N. Irani, Kuo I. Lin, Diane E. Griffin

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


The unique immunologic environment of the central nervous system (CNS) regulates most local inflammatory responses. In some circumstances, however, immune-mediated injury to the brain can occur. To understand how lymphocytes are regulated within the CNS during an inflammatory response that does not produce immunopathology, we have studied T cells isolated from the brains of mice with Sindbis virus (SV) encephalitis. Even though they express activation markers, these T cells are arrested in the cell cycle and do not proliferate in vitro. Altered phosphorylation of the retinoblastoma gene product, a critical cell cycle regulator, appears to mediate this effect. Furthermore, while brain-derived T cells generate IFN-γ, IL-4, and IL-10, these T cells are deficient in IL-2 production compared with peripheral T cells. This pattern of cytokine production occurs in cells that do not activate NF-κB normally. When T cells producing both IL-2 and IFN-γ are adoptively transferred into SV-infected mice, some of these cells traffic into the brain. Those that enter the brain selectively down-regulate IL-2 production over time. Since normal brain lipids can inhibit IL-2 production and T cell proliferation in vitro, these substances may mediate these same effects in vivo. 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 effect serves to prevent excessive local T cell reactivity. Whether and how this regulation might fail in the setting of autoimmune neurologic disease remains to be explored.

Original languageEnglish (US)
Pages (from-to)2318-2326
Number of pages9
JournalJournal of Immunology
Issue number5
StatePublished - Mar 1 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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