Abstract
Toxoplasma gondii forms tissue cysts in neurons and astrocytes in the brain to establish chronic infection, and astrocytes express the CXCL10 chemokine in chronically infected mice. Since chemokines mediate the migration of T cells to attack their targets, and since CXCL10 plays key roles in T cell-mediated control of the proliferation of tachyzoites (the acute stage form) of T. gondii during the acute stage of infection, we examined whether CXCL10 is involved in recruiting anti-cyst CD8(+) cytotoxic T cells to eliminate the cysts in their brains. We employed adoptive transfer of CD8(+) immune T cells to infected, T cell-deficient SCID and RAG1(-/-) mice in combination with blocking CXCL10 activity by neutralizing antibody or a deletion of this chemokine gene. The treatment of chronically infected (infected and treated with sulfadiazine) SCID mice with the anti-CXCL10 antibody did not inhibit the recruitment of the transferred CD8(+) T cells into their brains and the removal of cerebral T. gondii cysts by the T cells. In addition, the neutralization of CXCL10 did not reduce the cerebral expression of mRNA for the mediators (perforin and granzyme B [GzmB]) of the cytotoxic activity of CD8(+) T cells in the SCID mice. Consistently, the adoptive transfer of CD8(+) immune T cells to chronically infected RAG1(-/-)CXCL10(-/-) mice did not show any defects in recruiting the CD8(+) T cells into their brains and eliminating the cysts when compared to infected RAG1(-/-) mice. The former rather displayed enhanced cyst removal with increased cerebral expression of GzmB mRNA. These results indicate that the absence of CXCL10 activity does not ablate the capability of CD8(+) cytotoxic T cells to migrate into the brain and eliminate T. gondii cysts from the brains of chronically infected mice. These results also suggest that the immune system utilizes distinct chemokines to control T. gondii depending on the two different life cycle stages, tachyzoite and cyst, of this protozoan parasite.