Ha. Doyle et Jw. Murphy, Role of the C-C chemokine, TCA3, in the protective anticryptococcal cell-mediated immune response, J IMMUNOL, 162(8), 1999, pp. 4824-4833
Activated T lymphocytes play a crucial role in orchestrating cellular infil
tration during a cell-mediated immune (CMI) reaction. TCA3, a C-C chemokine
, is produced by Ag-activated T cells and is chemotactic for neutrophils an
d macrophages, two cell types in a murine CMI reaction. Using a gelatin spo
nge model for delayed-type hypersensitivity (DTH), we show that TCA3 is a c
omponent of the expression phase of an anticryptococcal CMI response in mic
e. TCA3 mRNA levels are augmented in anti-cryptococcal DTH reactions at the
same time peak influxes of neutrophils and lymphocytes are observed. Neutr
alization of TCA3 in immunized mice results in reduced numbers of neutrophi
ls and lymphocytes at DTH reaction sites. However, when rTCA3 is injected i
nto sponges in naive mice, only neutrophils are attracted into the sponges,
indicating TCA3 is chemotactic for neutrophils, but not lymphocytes. We sh
ow that TCA3 is indirectly attracting lymphocytes into DTH-reactive sponges
by affecting at least one other chemokine that is chemotactic for lymphocy
tes. Of the lymphocyte-attracting chemokines assessed, monocyte-chemotactic
protein-1 and macrophage-inflammatory protein-1 alpha (MIP-1 alpha), only
MIP-1 alpha was reduced when TCA3 was neutralized, indicating that TCA3 aff
ects the levels of MIP-1 alpha, which attracts lymphocytes into the sponges
. TCA3 also plays a role in protection against Cryptococcus neoformans in t
he lungs and brains of infected mice, as evidenced by the fact that neutral
ization of TCA3 results in increased C. neoformans CFU in those two organs.