Characteristics and critical function of CD8+ T cells in the Toxoplasma-infected brain

Abstract

The rise of the AIDS epidemic made the requirement for T cells in our continuous protection from pathogens critically apparent. The striking frequency with which AIDS patients exhibited profound neurological pathologies brought attention to many chronic infections that are latent within theimmune-privileged CNS. One of the most common lethal opportunistic infections of these patients was with the protozoan parasite, Toxoplasma gondii. Reactivation of Toxoplasma cysts within the brain causes massive tissue destruction evidenced as multiple ring-enhancing lesions on MRI and is called Toxoplasmic encephalitis (TE). TE is not limited to AIDS patients, but rather is a risk for all severely immunocompromised patients, including recipients of chemotherapy or transplant recipients. The lessons learned from these patient populations are supported by T cell depletion studies in mice. Such experiments have demonstrated that CD4+ and CD8+ T cells are required for protection against TE. Although it is clear that these T cell subsets work synergistically to fight infection, much evidence has been generated that suggests CD8+ T cells play a dominant role in protection during chronic toxoplasmosis. . In other models of CNS inflammation, such as intracerebral infection with LCMV and experimental autoimmune encephalomyelitis (EAE), infiltration of T cells into the brain is harmful and even fatal. In the brain of the immunocompetent host, the well-regulated T cell response to Toxoplasma gondii is therefore an ideal model to understand a controlled inflammatory response to CNS infection. This review will examine our current understanding of CD8+ T cells in the CNS during T. gondii infection in regards to the 1) mechanisms governing entry into the brain, 2) cues that dictate behavior within the brain, and 3) the functional and phenotypic properties exhibited by these cells

Revisiting the Mechanisms of CNS Immune Privilege

“…In addition, several pathogens establish chronic infections of the CNS, including cytomegalovirus, JC virus, herpes simplex virus, and Toxoplasma gondii. Ongoing immune responses are required to prevent lethal reactivation of these diseases, yet the mechanisms by which antigens from these pathogens were able to maintain a continuous peripheral immune response has not been determined [89][90][91][92]. The CNS lymphatics may be centrally involved in the maintenance of the immune response to these opportunistic pathogens of the CNS.…”

Infectious immunity in the central nervous system and brain function

“…CNS invasion by T. gondii 121 leads to infection of all neural cell types, most of which are promptly cleared of parasite via astrocyte and microglial expression of T cell chemoattractants CCL5, CXCL9 and CXCL10, that recruit IFN-γ-expressing CD4 + and CD8 + T cells directed at T. gondii antigens 122 . Neurons remain latently infected with slowly replicating bradyzoites throughout the life of the host.…”

Development of a risk scoring system for prognostication in HIV-related toxoplasma encephalitis

“…The prevalence of co-infection with Toxoplasma gondii and HIV ranges from 25.1-60.7% in different countries (10). The mortality of HIV-associated TE during hospitalization, with appropriate antitoxoplasma treatment, may be up to 30% (4).…”