Removal of Toxoplasma gondii Cysts from the Brain by Perforin-Mediated Activity of CD8+ T Cells

Am J Pathol. 2010 Feb 18. [Epub ahead of print]

Removal of Toxoplasma gondii Cysts from the Brain by Perforin-Mediated Activity of CD8+ T Cells

Suzuki Y, Wang X, Jortner BS, Payne L, Ni Y, Michie SA, Xu B, Kudo T, Perkins S.

From the Department of Biomedical Sciences,* Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, Virginia; the Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, Lexington, Kentucky; and the Department of Pathology, Stanford University School of Medicine, Stanford, California.

Chronic infection with Toxoplasma gondii is one of the most common parasitic infections in humans. Formation of tissue cysts is the basis of persistence of the parasite in infected hosts, and this cyst stage has generally been regarded as untouchable. Here we provide the first evidence that the immune system can eliminate T. gondii cysts from the brains of infected hosts when immune T cells are transferred into infected immunodeficient animals that have already developed large numbers of cysts. This T cell-mediated immune process was associated with accumulation of microglia and macrophages around tissue cysts. CD8(+) immune T cells possess a potent activity to remove the cysts. The initiation of this process by CD8(+) T cells does not require the production of interferon-gamma, the major mediator to prevent proliferation of tachyzoites during acute infection, but does require perforin. These results suggest that CD8(+) T cells induce elimination of T. gondii cysts through their perforin-mediated cytotoxic activity. Our findings provide a new mechanism of the immune system to fight against chronic infection with T. gondii and suggest a possibility of developing a novel vaccine to eliminate cysts from patients with chronic infection and to prevent the establishment of chronic infection after a newly acquired infection.

PMID: 20167872 [PubMed - as supplied by publisher]