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The NKG2D ligand MULT‐1 is upregulated in the brain following infection with Theiler's murine encephalomyelitis virus
Author(s) -
Deb Chandra,
Howe Charles L
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb24-b
Subject(s) - nkg2d , ctl* , immune system , mhc class i , immunology , biology , viral load , cytotoxic t cell , downregulation and upregulation , virus , acquired immune system , major histocompatibility complex , virology , cd8 , gene , in vitro , biochemistry
Natural killer cells (NKC) and cytotoxic T lymphocytes (CTL) express NKG2D, a lectin‐like molecule that serves as a direct stimulatory receptor in the innate immune system and as a co‐stimulatory receptor in the adaptive system. In mice, the ligands for NKG2D are stress‐inducible molecules such as Rae‐1, H‐60 and MULT‐1. These MHC class I‐like molecules are generally absent in normal tissues but are upregulated by inflammation and virus infection. We have found that acute intracerebral infection with the Theiler's murine encephalomyelitis virus (TMEV) elicits robust infiltration of NKG2D‐positive CTL and NKC into the brain coincident with the zenith and resolution of viral load. Likewise, using quantitative RT‐PCR we found that MULT‐1 was upregulated coincident with the peak of viral load while Rae‐1 (only epsilon and delta tested) and H‐60 remained undetectable. Therefore, we hypothesized that CTL and NKC recognition of MULT‐1 on neurons is required for efficient viral clearance. However, in vivo immunodepletion of NKC and CTL beginning one day prior to infection and continuing throughout the first 3 weeks postinfection did not prevent efficient viral clearance despite greater than 90% reduction in NKG2D‐positive cells in the brain immune infiltrate as assessed by flow cytometry. Thus, the role of MULT‐1 expression following TMEV infection remains unclear and experiments are ongoing to determine the cellular locus of MULT‐1 expression and recognition. This work was supported by grant RG3636 from the National Multiple Sclerosis Society and by Donald and Frances Herdrich.