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Human CD8+ T Cells Clear Cryptosporidium parvum from Infected Intestinal Epithelial Cells

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  • 1 Division of Infectious Diseases, Department of Internal Medicine, Department of Microbiology, University of Texas Medical Branch, Galveston, Texas; Center for Electromechanics, University of Texas, Austin, Texas; Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts
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Intracellular protozoans of the genus Cryptosporidium are a major cause of diarrheal illness worldwide, especially in immunocompromised individuals. CD4+ T cells and interferon-gamma are key factors in the control of cryptosporidiosis in human and murine models. Previous studies led us to hypothesize that CD8+ T cells contribute to clearance of intestinal epithelial Cryptosporidium infection in humans. We report here that antigen expanded sensitized CD8+ T cells reduce the parasite load in infected intestinal epithelial cell cultures and lyse infected intestinal epithelial cells. These effects are most likely mediated by the release of cytotoxic granules. Elimination of parasites seems to require antigen presentation through both human leukocyte antigen (HLA)-A and HLA-B. These data suggest that cytotoxic CD8+ T cells play a role in clearing Cryptosporidium from the intestine, a previously unrecognized feature of the human immune response against this parasite.

Author Notes

*Address correspondence to A. Clinton White Jr., Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555. E-mail: acwhite@utmb.edu

Authors' addresses: Birte Pantenburg, Alejandro Castellanos-Gonzalez, and A. Clinton White Jr., Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, E-mails: birte.pantenburg@upch.pe, alcastel@utmb.edu, and acwhite@utmb.edu. Sara M. Dann and Dorothy E. Lewis, Division of Infectious Diseases, Department of Internal Medicine, and Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, E-mails: smdann@utmb.edu and dolewis@utmb.edu. Rhykka L. Connelly, Center for Electromechanics, University of Texas, Austin, TX, E-mail: r.connelly@cem.utexas.edu. Honorine D. Ward, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA, E-mail: hward@tuftsmedicalcenter.org.

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