T GONDII--ROLE OF INTRAEPITHELIAL LYMPHOCYTE HOMING

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This collaborative application is focused on the role of mucosal immunity to the opportunistic pathogen, Toxoplasma gondii. This orally- acquire intracellular parasite is the most frequent CNS infection in those with AIDS and is a major source of congenital infection in the newborn. In the past two years, these researchers have observed that intestinal-derived intraepithelial lymphocytes (IEL's) are important modulators of host immunity to this parasite CD8+ IEL's isolated from the intestine of acutely infected mice confer 100 percent protection against parasite challenge when adoptively transferred into naive recipients. Preliminary observations from their laboratories suggest that the IEL's home to the intestine and, perhaps, traffic to other organs following challenge. The first specific aim of this project is to determine if localization of the IEL's to the intestine is a requirement for the induction of host immunity. The researchers will determine whether these IEL's express homing receptors and whether blocking of these receptors inhibits their ability to induce protection. The second specific aim is to establish if the IEL's traffic outside the intestine. In particular, the researchers will evaluated whether the IEL provide long-term immunity, and whether this is associated with the expression of a memory phenotype on the IEL. The last objective is to determine whether the migratory IEL's can prevent reactivation in the chronically infected host. Together, these findings will allow the researchers to determine, further, the immunologic function of mucosal immunity against this parasite.