In Vitro Correlates ofLd-Restricted Resistance to Toxoplasmic Encephalitis and Their Critical Dependence on Parasite Strain

Abstract

Resistance to murine toxoplasmic encephalitis has been precisely and definitively mapped to the Ld class I gene. Consistent with this, CD8+ T cells can adoptively transfer resistance to toxoplasmic encephalitis. However, cytotoxic CD8+ T cells, capable of killing class I-matched, infected target cells, are generated during the course of Toxoplasma gondii infection even in mice lacking the Ld gene. Ld-restricted killing could not be demonstrated, and the functional correlate of the Ld gene has therefore remained elusive. Herein, Ld-restricted killing of T. gondii-infected target cells is demonstrated for the first time. Ld-restricted killing is critically dependent on the strain of T. gondii and is observed with all the derivatives of type II strains tested, but not with a type I strain. These results have important implications for vaccine development.

The Induction and Kinetics of Antigen-Specific CD8 T Cells Are Defined by the Stage Specificity and Compartmentalization of the Antigen in Murine Toxoplasmosis

“…In fact, T. gondii has recently been probed for its potential to serve as a vaccine vector in murine malaria (40). However, the application of T. gondii as a vaccine vector might potentially be limited by the fact that resistance to T. gondii as well as strong and persisting Ag-specific CD8 T cell responses are genetically restricted to L d , as observed in the present and previous studies (8,41).…”

Isolation and Genotyping of Toxoplasma Gondii Causing Fatal Systemic Toxoplasmosis in an Immunocompetent 10-Year-Old Cat

“…7 During the chronic phase of infection, the L d -restricted cytolytic activity was elicited by type II but not by type I T. gondii. 18 Moreover, certain gene polymorphisms are associated with a higher susceptibility to clinical infection with T. gondii in human beings. Some of these are located within the MHC complex, 24 but others were found in unrelated loci.…”

Protective Effect of Vaccination with Toxoplasma Lysate Antigen and CpG as an Adjuvant against Toxoplasma gondii in Susceptible C57BL/6 Mice

“…This could be explained by the lack of the cellular arm of immunity, which is necessary to control toxoplasmosis (17,19). Furthermore the high IL-4 serum levels encountered in this group at the end of the observation period point to the possibility of a Th2 immune shift, an inhibitory response against clearance of intracellular pathogens.…”

“…Since the production of these cytokines represents an early event in the natural defense mechanisms against toxoplasma (5,16,37), it is likely that if we primed mice with CpG/TLA before challenge, it would be able to control infection. Furthermore, CpG enhances cytolytic CD8 ϩ T cells, which are involved as well in protection against toxoplasma (17,19).…”