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* Max Planck Institute for Infection Biology, Berlin, Germany; and
Amgen, Inc., Thousand Oaks, CA 91320
The inducible costimulator protein (ICOS) was recently identified
as a costimulatory molecule for T cells. Here we analyze the role of
ICOS for the acquired immune response of mice against the intracellular
bacterium Listeria monocytogenes. During oral L.
monocytogenes infection, low levels of ICOS expression were
detected by extracellular and intracellular Ab staining of
Listeria-specific CD4+ and CD8+ T cells.
Blocking of ICOS signaling with a soluble ICOS-Ig fusion protein
markedly impaired the Listeria-specific T cell responses. Compared with
control mice, the ICOS-Ig treated mice generated significantly reduced
numbers of Listeria-specific CD8+ T cells in spleen and
liver, as determined by tetramer and intracellular cytokine staining.
In contrast, the specific CD8+ T cell response in the
intestinal mucosa did not appear to be impaired by the ICOS-Ig
treatment. Analysis of the CD4+ T cell response revealed
that ICOS-Ig treatment also affected the specific CD4+ T
cell response. When restimulated with listerial Ag in vitro, reduced
numbers of CD4+ T cells from infected and ICOS-Ig-treated
mice responded with IFN-
production. The impaired acquired immune
response in ICOS-Ig treated mice was accompanied by their increased
susceptibility to L. monocytogenes infection. ICOS-Ig
treatment drastically enhanced bacterial titers, and a large fraction
of mice succumbed to the otherwise sublethal dose of infection. Thus,
ICOS costimulation is crucial for protective immunity against the
intracellular bacterium L.
monocytogenes.
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