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Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190
Activated T lymphocytes play a crucial role in orchestrating
cellular infiltration during a cell-mediated immune (CMI) reaction.
TCA3, a C-C chemokine, is produced by Ag-activated T cells and is
chemotactic for neutrophils and macrophages, two cell types in a murine
CMI reaction. Using a gelatin sponge model for delayed-type
hypersensitivity (DTH), we show that TCA3 is a component of the
expression phase of an anticryptococcal CMI response in mice. TCA3 mRNA
levels are augmented in anticryptococcal DTH reactions at the same
time peak influxes of neutrophils and lymphocytes are observed.
Neutralization of TCA3 in immunized mice results in reduced numbers of
neutrophils and lymphocytes at DTH reaction sites. However, when rTCA3
is injected into sponges in naive mice, only neutrophils are attracted
into the sponges, indicating TCA3 is chemotactic for neutrophils, but
not lymphocytes. We show that TCA3 is indirectly attracting lymphocytes
into DTH-reactive sponges by affecting at least one other chemokine
that is chemotactic for lymphocytes. Of the two lymphocyte-attracting
chemokines assessed, monocyte-chemotactic protein-1 and
macrophage-inflammatory protein-1
(MIP-1), only MIP-1 was
reduced when TCA3 was neutralized, indicating that TCA3 affects the
levels of MIP-1, which attracts lymphocytes into the sponges. TCA3
also plays a role in protection against Cryptococcus
neoformans in the lungs and brains of infected mice, as
evidenced by the fact that neutralization of TCA3 results in increased
C. neoformans CFU in those two
organs.
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