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In Vitro Correlates of L^d-Restricted Resistance to Toxoplasmic Encephalitis and Their Critical Dependence on Parasite Strain¹

Jennifer J. Johnson^*, Craig W. Roberts^2,*, Constance Pope^3,*, Fiona Roberts^4,*, Michael J. Kirisits^*, Randee Estes^*, Ernest Mui^*, Tim Krieger^*, Charles R. Brown^5,*, Jim Forman and Rima McLeod^6,*

^* University of Chicago, Chicago, IL 60637; Michael Reese Hospital and Medical Center, Chicago, IL 60616; and University of Texas Southwestern Medical School, Dallas, TX 75235

Resistance to murine toxoplasmic encephalitis has been precisely and definitively mapped to the L^d 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 L^d gene. L^d-restricted killing could not be demonstrated, and the functional correlate of the L^d gene has therefore remained elusive. Herein, L^d-restricted killing of T. gondii-infected target cells is demonstrated for the first time. L^d-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.

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