{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:35:35Z","timestamp":1790382935417,"version":"4.1.0"},"reference-count":39,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,4]]},"abstract":"<jats:p>Intracellular protozoans of the genus <jats:italic>Cryptosporidium<\/jats:italic> are a major cause of diarrheal illness worldwide, especially in immunocompromised individuals. CD4<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> T cells contribute to clearance of intestinal epithelial <jats:italic>Cryptosporidium<\/jats:italic> infection in humans. We report here that antigen expanded sensitized CD8<jats:sup>+<\/jats:sup> 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<jats:sup>+<\/jats:sup> T cells play a role in clearing <jats:italic>Cryptosporidium<\/jats:italic> from the intestine, a previously unrecognized feature of the human immune response against this parasite.<\/jats:p>","DOI":"10.4269\/ajtmh.2010.09-0590","type":"journal-article","created":{"date-parts":[[2010,3,26]],"date-time":"2010-03-26T23:33:07Z","timestamp":1269646387000},"page":"600-607","source":"Crossref","is-referenced-by-count":43,"title":["Human CD8+ T Cells Clear Cryptosporidium parvum from Infected Intestinal Epithelial Cells"],"prefix":"10.4269","volume":"82","author":[{"given":"Birte","family":"Pantenburg","sequence":"first","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Castellanos-Gonzalez","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara M.","family":"Dann","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhykka L.","family":"Connelly","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothy E.","family":"Lewis","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honorine D.","family":"Ward","sequence":"additional","affiliation":[{"name":"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"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Clinton White","sequence":"additional","affiliation":[{"name":"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, 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protozoan Cryptosporidium","volume":"192","author":"Dann","year":"2005"},{"key":"R6","series-title":"Infect Immun","first-page":"961","article-title":"New mouse models for chronic Cryptosporidium infection in immunodeficient hosts","volume":"58","author":"Ungar","year":"1990"},{"key":"R7","series-title":"Infect Immun","first-page":"697","article-title":"Susceptibility of major histocompatibility complex (MHC) class I- and MHC class II-deficient mice to Cryptosporidium parvum infection","volume":"62","author":"Aguirre","year":"1994"},{"key":"R8","series-title":"Infect Immun","first-page":"8425","article-title":"An early intestinal mucosal source of gamma interferon is associated with resistance to and control of Cryptosporidium parvum infection in mice","volume":"73","author":"Leav","year":"2005"},{"key":"R9","series-title":"J Parasitol","first-page":"1045","article-title":"Susceptibility differences to Cryptosporidium parvum infection in two strains of gamma interferon knockout mice","volume":"84","author":"Mead","year":"1998"},{"key":"R10","series-title":"Infect Immun","first-page":"3548","article-title":"Gamma interferon functions in resistance to Cryptosporidium parvum infection in severe combined immunodeficient mice","volume":"61","author":"Chen","year":"1993"},{"key":"R11","series-title":"Infect Immun","first-page":"4761","article-title":"Profiles of healing and nonhealing Cryptosporidium parvum infection in C57BL\/6 mice with functional B and T lymphocytes: the extent of gamma interferon modulation determines the outcome of infection","volume":"65","author":"Theodos","year":"1997"},{"key":"R12","series-title":"J Infect Dis","first-page":"211","article-title":"Crude extract and recombinant protein of Cryptosporidium parvum oocysts induce proliferation of human peripheral blood mononuclear cells in vitro","volume":"172","author":"Gomez-Morales","year":"1995"},{"key":"R13","series-title":"J Infect Dis","first-page":"967","article-title":"Cytokine profile induced by Cryptosporidium antigen in peripheral blood mononuclear cells from immunocompetent and immunosuppressed persons with cryptosporidiosis","volume":"179","author":"Gomez-Morales","year":"1999"},{"key":"R14","series-title":"J Infect Dis","first-page":"701","article-title":"Interferon-gamma expression in jejunal biopsies in experimental human cryptosporidiosis correlates with prior sensitization and control of oocyst excretion","volume":"181","author":"White","year":"2000"},{"key":"R15","series-title":"Am J Trop Med Hyg","first-page":"583","article-title":"Seropositive human subjects produce interferon gamma after stimulation with recombinant Cryptosporidium hominis gp15","volume":"77","author":"Preidis","year":"2007"},{"key":"R16","series-title":"J Infect Dis","first-page":"474","article-title":"Association between Cryptosporidium infection and human leukocyte antigen class I and class II alleles","volume":"197","author":"Kirkpatrick","year":"2008"},{"key":"R17","series-title":"J Parasitol","first-page":"1350","article-title":"Quantitative tracking of Cryptosporidium infection in cell culture with CFSE","volume":"92","author":"Feng","year":"2006"},{"key":"R18","series-title":"N Engl J Med","first-page":"855","article-title":"The infectivity of Cryptosporidium parvum in healthy volunteers","volume":"332","author":"DuPont","year":"1995"},{"key":"R19","series-title":"Infect Immun","first-page":"4108","article-title":"Molecular cloning and expression of a gene encoding Cryptosporidium parvum glycoproteins gp40 and gp15","volume":"68","author":"Cevallos","year":"2000"},{"key":"R20","series-title":"Infect Immun","first-page":"4117","article-title":"Cloning and sequence analysis of a highly polymorphic Cryptosporidium parvum gene encoding a 60-kilodalton glycoprotein and characterization of its 15- and 45-kilodalton zoite surface antigen products","volume":"68","author":"Strong","year":"2000"},{"key":"R21","series-title":"Infect Immun","first-page":"3881","article-title":"Analysis of sequence diversity at the highly polymorphic Cpgp40\/15 locus among Cryptosporidium isolates from human immunodeficiency virus-infected children in South Africa","volume":"70","author":"Leav","year":"2002"},{"key":"R22","series-title":"Appl Environ Microbiol","first-page":"106","article-title":"Comparison of primers and optimization of PCR conditions for detection of Cryptosporidium parvum and Giardia lamblia in water","volume":"63","author":"Rochelle","year":"1997"},{"key":"R23","series-title":"Clin Exp Immunol","first-page":"259","article-title":"Interleukin-12 up-regulates perforin- and Fas-mediated lymphokine-activated killer activity by intestinal intraepithelial lymphocytes","volume":"138","author":"Ebert","year":"2004"},{"key":"R24","series-title":"Hum Immunol","first-page":"1195","article-title":"Isolation of broadly reactive, tumor-specific, HLA Class-I restricted CTL from blood lymphocytes of a breast cancer patient","volume":"60","author":"Verdegaal","year":"1999"},{"key":"R25","series-title":"Br J Cancer","first-page":"72","article-title":"Pooled peptides from HER-2\/neu-overexpressing primary ovarian tumours induce CTL with potent antitumour responses in vitro and in vivo","volume":"92","author":"Gritzapis","year":"2005"},{"key":"R26","series-title":"J Invest Dermatol","first-page":"994","article-title":"Functional inhibitory receptors expressed by a cutaneous T cell lymphoma-specific cytolytic clonal T cell population","volume":"115","author":"Bagot","year":"2000"},{"key":"R27","series-title":"Clin Vaccine Immunol","first-page":"1616","article-title":"Enhancement of human antigen-specific memory T-cell responses by interleukin-7 may improve accuracy in diagnosing tuberculosis","volume":"15","author":"Feske","year":"2008"},{"key":"R28","series-title":"J 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