CD4-Positive T Cell-Mediated Neuroprotection Requires Dual Compartment Antigen Presentation

Susanna C. Byram, Monica J. Carson, Cynthia A. DeBoy, Craig J. Serpe, Virginia M. Sanders, Kathryn J. Jones

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

Our laboratory discovered that CD4-positive (CD4+) T cells of the immune system convey transitory neuroprotection to injured mouse facial motoneurons (FMNs) (Serpe et al., 1999, 2000, 2003). A fundamental question in the mechanisms responsible for neuroprotection concerns the identity of the cell(s) that serves as the antigen-presenting cell (APC) to activate the CD4+ T cells. Here, we first establish that CD4+ T cells reactive to non-CNS antigen fail to support FMN survival and, second, demonstrate a two-compartment model of CD4+ T cell activation. Mouse bone marrow (BM) chimeras were developed that discriminate between resident antigen-presenting host cell and BM-derived antigen-presenting donor cell expression of major histocompatibility complex II within central and peripheral compartments, respectively. After facial nerve transection, neither compartment alone is sufficient to result in activated CD4+ T cell-mediated FMN survival. Rather, CD4+ T cell-mediated neuroprotection appears to depend on both resident microglial cells in the central compartment and a BM-derived APC in the peripheral compartment. This is the first in vivo report demonstrating a neuroprotective mechanism requiring APC functions by resident (i.e., parenchymal) microglial cells.

Original languageEnglish (US)
Pages (from-to)4333-4339
Number of pages7
JournalJournal of Neuroscience
Volume24
Issue number18
DOIs
StatePublished - May 5 2004

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Keywords

  • Antigen-presenting cell
  • CD4 T lymphocytes
  • Chimera mice
  • Facial motoneuron
  • Microglia
  • Motoneuron survival
  • Neuro-immune interactions

ASJC Scopus subject areas

  • Neuroscience(all)

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