Role of the C-C chemokine, TCA3, in the protective anticryptococcal cell-mediated immune response

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.