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T Cell-Deficient Mice Have a Down-Regulated CD8⁺ T Cell Immune Response Against Encephalitozoon cuniculi Infection¹

Magali Moretto^,, Brigit Durell, Joseph D. Schwartzman and Imtiaz A. Khan^2,*,,

Departments of ^* Medicine, Microbiology, and Pathology, Dartmouth Medical School, Lebanon, NH 03756; and Department of Microbiology, Immunology, and Parasitology, Louisiana State University Medical Center, New Orleans, LA 70112

T cells have been reported to play an essential effector role during the early immune response against a wide variety of infectious agents. Recent studies have suggested that the T cell subtype may also be important for the induction of adaptive immune response against certain microbial pathogens. In the present study, an early increase of T cells during murine infection with Encephalitozoon cuniculi, an intracellular parasite, was observed. The role of T cells against E. cuniculi infection was further evaluated by using gene-knockout mice. Mice lacking T cells were susceptible to E. cuniculi infection at high challenge doses. The reduced resistance of ^-/- mice was attributed to a down-regulated CD8⁺ immune response. Compared with parental wild-type animals, suboptimal Ag-specific CD8⁺ T cell immunity against E. cuniculi infection was noted in ^-/- mice. The splenocytes from infected knockout mice exhibited a lower frequency of Ag-specific CD8⁺ T cells. Moreover, adoptive transfer of immune TCR⁺ CD8⁺ T cells from the ^-/- mice failed to protect naive CD8^-/- mice against a lethal E. cuniculi challenge. Our studies suggest that T cells, due to their ability to produce cytokines, are important for the optimal priming of CD8⁺ T cell immunity against E. cuniculi infection. This is the first evidence of a parasitic infection in which down-regulation of CD8⁺ T cell immune response in the absence of T cells has been demonstrated.

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