Pantenburg B, Dann SM, Wang HC, Robinson P, Castellanos-Gonzalez A, Lewis DE, White AC Jr, 2008. Intestinal immune response to human Cryptosporidium sp. infection. Infect Immun 76: 23–29.
Blanshard C, Jackson AM, Shanson DC, Francis N, Gazzard BG, 1992. Cryptosporidiosis in HIV-seropositive patients. Q J Med 85: 813–823.
Flanigan T, Whalen C, Turner J, Soave R, Toerner J, Havlir D, Kotler D, 1992. Cryptosporidium infection and CD4 counts. Ann Intern Med 116: 840–842.
Manabe YC, Clark DP, Moore RD, Lumadue JA, Dahlman HR, Belitsos PC, Chaisson RE, Sears CL, 1998. Cryptosporidiosis in patients with AIDS: correlates of disease and survival. Clin Infect Dis 27: 536–542.
Dann SM, Wang HC, Gambarin KJ, Actor JK, Robinson P, Lewis DE, Caillat-Zucman S, White AC Jr, 2005. Interleukin-15 activates human natural killer cells to clear the intestinal protozoan Cryptosporidium. J Infect Dis 192: 1294–1302.
Ungar BL, Burris JA, Quinn CA, Finkelman FD, 1990. New mouse models for chronic Cryptosporidium infection in immunodeficient hosts. Infect Immun 58: 961–969.
Aguirre SA, Mason PH, Perryman LE, 1994. Susceptibility of major histocompatibility complex (MHC) class I- and MHC class II-deficient mice to Cryptosporidium parvum infection. Infect Immun 62: 697–699.
Leav BA, Yoshida M, Rogers K, Cohen S, Godiwala N, Blumberg RS, Ward H, 2005. An early intestinal mucosal source of gamma interferon is associated with resistance to and control of Cryptosporidium parvum infection in mice. Infect Immun 73: 8425–8428.
Mead JR, You X, 1998. Susceptibility differences to Cryptosporidium parvum infection in two strains of gamma interferon knockout mice. J Parasitol 84: 1045–1048.
Chen W, Harp JA, Harmsen AG, Havell EA, 1993. Gamma interferon functions in resistance to Cryptosporidium parvum infection in severe combined immunodeficient mice. Infect Immun 61: 3548–3551.
Theodos CM, Sullivan KL, Griffiths JK, Tzipori S, 1997. 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. Infect Immun 65: 4761–4769.
Gomez-Morales MA, Ausiello CM, Urbani F, Pozio E, 1995. Crude extract and recombinant protein of Cryptosporidium parvum oocysts induce proliferation of human peripheral blood mononuclear cells in vitro. J Infect Dis 172: 211–216.
Gomez-Morales MA, La Rosa G, Ludovisi A, Onori AM, Pozio E, 1999. Cytokine profile induced by Cryptosporidium antigen in peripheral blood mononuclear cells from immunocompetent and immunosuppressed persons with cryptosporidiosis. J Infect Dis 179: 967–973.
White AC, Robinson P, Okhuysen PC, Lewis DE, Shahab I, Lahoti S, DuPont HL, Chappell CL, 2000. Interferon-gamma expression in jejunal biopsies in experimental human cryptosporidiosis correlates with prior sensitization and control of oocyst excretion. J Infect Dis 181: 701–709.
Preidis GA, Wang HC, Lewis DE, Castellanos-Gonzalez A, Rogers KA, Graviss EA, Ward HD, White AC Jr, 2007. Seropositive human subjects produce interferon gamma after stimulation with recombinant Cryptosporidium hominis gp15. Am J Trop Med Hyg 77: 583–585.
Kirkpatrick BD, Haque R, Duggal P, Mondal D, Larsson C, Peterson K, Akter J, Lockhart L, Khan S, Petri WA Jr, 2008. Association between Cryptosporidium infection and human leukocyte antigen class I and class II alleles. J Infect Dis 197: 474–478.
Feng H, Nie W, Bonilla R, Widmer G, Sheoran A, Tzipori S, 2006. Quantitative tracking of Cryptosporidium infection in cell culture with CFSE. J Parasitol 92: 1350–1354.
DuPont H, Chappell C, Sterling C, Okhuysen P, Rose J, Jabubowski W, 1995. The infectivity of Cryptosporidium parvum in healthy volunteers. N Engl J Med 332: 855–859.
Cevallos AM, Zhang X, Waldor MK, Jaison S, Zhou X, Tzipori S, Neutra MR, Ward HD, 2000. Molecular cloning and expression of a gene encoding Cryptosporidium parvum glycoproteins gp40 and gp15. Infect Immun 68: 4108–4116.
Strong WB, Gut J, Nelson RG, 2000. 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. Infect Immun 68: 4117–4134.
Leav BA, Mackay MR, Anyanwu A, O'Connor RM, Cevallos AM, Kindra G, Rollins NC, Bennish ML, Nelson RG, Ward HD, 2002. Analysis of sequence diversity at the highly polymorphic Cpgp40/15 locus among Cryptosporidium isolates from human immunodeficiency virus-infected children in South Africa. Infect Immun 70: 3881–3890.
Rochelle PA, De Leon R, Stewart MH, Wolfe RL, 1997. Comparison of primers and optimization of PCR conditions for detection of Cryptosporidium parvum and Giardia lamblia in water. Appl Environ Microbiol 63: 106–114.
Ebert EC, 2004. Interleukin-12 up-regulates perforin- and Fas-mediated lymphokine-activated killer activity by intestinal intraepithelial lymphocytes. Clin Exp Immunol 138: 259–265.
Verdegaal EM, Huinink DB, Hoogstraten C, Marijnissen AK, Gorsira MB, Claas FH, Osanto S, 1999. Isolation of broadly reactive, tumor-specific, HLA Class-I restricted CTL from blood lymphocytes of a breast cancer patient. Hum Immunol 60: 1195–1206.
Gritzapis AD, Perez SA, Baxevanis CN, Papamichail M, 2005. Pooled peptides from HER-2/neu-overexpressing primary ovarian tumours induce CTL with potent antitumour responses in vitro and in vivo. Br J Cancer 92: 72–79.
Bagot M, Martinvalet D, Echchakir H, Chabanette-Schirm F, Boumsell L, Bensussan A, 2000. Functional inhibitory receptors expressed by a cutaneous T cell lymphoma-specific cytolytic clonal T cell population. J Invest Dermatol 115: 994–999.
Feske M, Nudelman RJ, Medina M, Lew J, Singh M, Couturier J, Graviss EA, Lewis DE, 2008. Enhancement of human antigen-specific memory T-cell responses by interleukin-7 may improve accuracy in diagnosing tuberculosis. Clin Vaccine Immunol 15: 1616–1622.
Kataoka T, Shinohara N, Takayama H, Takaku K, Kondo S, Yonehara S, Nagai K, 1996. Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity. J Immunol 156: 3678–3686.
Gomez-Morales MA, Ausiello CM, Guarino A, Urbani F, Spagnuolo MI, Pignata C, Pozio E, 1996. Severe, protracted intestinal cryptosporidiosis associated with interferon γ deficiency: pediatric case report. Clin Infect Dis 22: 848–850.
Pollok RC, Farthing MJ, Bajaj-Elliott M, Sanderson IR, McDonald V, 2001. Interferon gamma induces enterocyte resistance against infection by the intracellular pathogen Cryptosporidium parvum. Gastroenterology 120: 99–107.
Salerno-Goncalves R, Pasetti MF, Sztein MB, 2002. Characterization of CD8(+) effector T cell responses in volunteers immunized with Salmonella enterica serovar Typhi strain Ty21a typhoid vaccine. J Immunol 169: 2196–2203.
Stegelmann F, Bastian M, Swoboda K, Bhat R, Kiessler V, Krensky AM, Roellinghoff M, Modlin RL, Stenger S, 2005. Coordinate expression of CC chemokine ligand 5, granulysin, and perforin in CD8+ T cells provides a host defense mechanism against Mycobacterium tuberculosis. J Immunol 175: 7474–7483.
Migueles SA, Laborico AC, Shupert WL, Sabbaghian MS, Rabin R, Hallahan CW, Van Baarle D, Kostense S, Miedema F, McLaughlin M, Ehler L, Metcalf J, Liu S, Connors M, 2002. HIV-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol 3: 1061–1068.
Jabri B, Ebert E, 2007. Human CD8+ intraepithelial lymphocytes: a unique model to study the regulation of effector cytotoxic T lymphocytes in tissue. Immunol Rev 215: 202–214.
Rodriguez-Juan C, Perez-Blas M, Valeri AP, Aguilera N, Arnaiz-Villena A, Pacheco-Castro A, Martin-Villa JM, 2001. Cell surface phenotype and cytokine secretion in Caco-2 cell cultures: increased RANTES production and IL-2 transcription upon stimulation with IL-1beta. Tissue Cell 33: 570–579.
Chavez-Galan L, Arenas-Del Angel MC, Zenteno E, Chavez R, Lascurain R, 2009. Cell death mechanisms induced by cytotoxic lymphocytes. Cell Mol Immunol 6: 15–25.
Castellanos-Gonzalez A, Yancey LS, Wang HC, Pantenburg B, Liscum KR, Lewis DE, White AC Jr, 2008. Cryptosporidium infection of human intestinal epithelial cells increases expression of osteoprotegerin: a novel mechanism for evasion of host defenses. J Infect Dis 197: 916–923.
Stenger S, Hanson DA, Teitelbaum R, Dewan P, Niazi KR, Froelich CJ, Ganz T, Thoma-Uszynski S, Melian A, Bogdan C, Porcelli SA, Bloom BR, Krensky AM, Modlin RL, 1998. An antimicrobial activity of cytolytic T cells mediated by granulysin. Science 282: 121–125.
Endsley JJ, Torres AG, Gonzales CM, Kosykh VG, Motin VL, Peterson JW, Estes DM, Klimpel GR, 2009. Comparative antimicrobial activity of granulysin against bacterial biothreat agents. Open Microbiol J 3: 92–96.
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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.
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: email@example.com, firstname.lastname@example.org, and email@example.com. 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: firstname.lastname@example.org and email@example.com. Rhykka L. Connelly, Center for Electromechanics, University of Texas, Austin, TX, E-mail: firstname.lastname@example.org. Honorine D. Ward, Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA, E-mail: email@example.com.