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. 1997 Jan;65(1):185–190. doi: 10.1128/iai.65.1.185-190.1997

Activation of intestinal intraepithelial T lymphocytes in calves infected with Cryptosporidium parvum.

C R Wyatt 1, E J Brackett 1, L E Perryman 1, A C Rice-Ficht 1, W C Brown 1, K I O'Rourke 1
PMCID: PMC174574  PMID: 8975910

Abstract

The objective of this study was to identify disease-related changes in lymphocyte populations within ileal mucosae of calves with cryptosporidiosis. Groups of five neonatal calves were orally infected at 3 days of age with 10(8) oocysts and maintained in enteric-pathogen-free conditions until clinical disease was established or until the animals had recovered from disease. Age-matched uninfected calves were used for comparison. Ileal mucosal lymphocytes were collected, quantitated, and phenotyped to determine whether changes in lymphocyte composition occurred in infected animals. We observed significantly larger numbers of intraepithelial CD8+ T lymphocytes in ileal mucosae from acutely infected calves compared with those from control animals. In addition, a proportion of intraepithelial CD4+ T cells from acutely infected calves coexpressed CD25, whereas there was an absence of coexpressed CD25 on CD4+ T cells from control calves. Ex vivo reverse transcriptase PCR of RNA from intraepithelial lymphocytes from control calves showed a cytokine expression pattern consisting of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), while intraepithelial lymphocytes from calves with cryptosporidiosis expressed IFN-gamma but not TNF-alpha. Together, the results indicate that changes occur in the ileal intraepithelial lymphocyte population coincidently with Cryptosporidium parvum-induced enteric disease.

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Selected References

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  1. Adams R. B., Planchon S. M., Roche J. K. IFN-gamma modulation of epithelial barrier function. Time course, reversibility, and site of cytokine binding. J Immunol. 1993 Mar 15;150(6):2356–2363. [PubMed] [Google Scholar]
  2. Aguirre S. A., Mason P. H., Perryman L. E. Susceptibility of major histocompatibility complex (MHC) class I- and MHC class II-deficient mice to Cryptosporidium parvum infection. Infect Immun. 1994 Feb;62(2):697–699. doi: 10.1128/iai.62.2.697-699.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barrett T. A., Gajewski T. F., Danielpour D., Chang E. B., Beagley K. W., Bluestone J. A. Differential function of intestinal intraepithelial lymphocyte subsets. J Immunol. 1992 Aug 15;149(4):1124–1130. [PubMed] [Google Scholar]
  4. Bjorneby J. M., Hunsaker B. D., Riggs M. W., Perryman L. E. Monoclonal antibody immunotherapy in nude mice persistently infected with Cryptosporidium parvum. Infect Immun. 1991 Mar;59(3):1172–1176. doi: 10.1128/iai.59.3.1172-1176.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bjorneby J. M., Riggs M. W., Perryman L. E. Cryptosporidium parvum merozoites share neutralization-sensitive epitopes with sporozoites. J Immunol. 1990 Jul 1;145(1):298–304. [PubMed] [Google Scholar]
  6. Bonneville M., Janeway C. A., Jr, Ito K., Haser W., Ishida I., Nakanishi N., Tonegawa S. Intestinal intraepithelial lymphocytes are a distinct set of gamma delta T cells. Nature. 1988 Dec 1;336(6198):479–481. doi: 10.1038/336479a0. [DOI] [PubMed] [Google Scholar]
  7. Brown W. C., Woods V. M., Chitko-McKown C. G., Hash S. M., Rice-Ficht A. C. Interleukin-10 is expressed by bovine type 1 helper, type 2 helper, and unrestricted parasite-specific T-cell clones and inhibits proliferation of all three subsets in an accessory-cell-dependent manner. Infect Immun. 1994 Nov;62(11):4697–4708. doi: 10.1128/iai.62.11.4697-4708.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cerretti D. P., McKereghan K., Larsen A., Cosman D., Gillis S., Baker P. E. Cloning, sequence, and expression of bovine interferon-gamma. J Immunol. 1986 Jun 15;136(12):4561–4564. [PubMed] [Google Scholar]
  9. Chapekar M. S., Glazer R. I. The synergistic cytocidal effect produced by immune interferon and tumor necrosis factor in HT-29 cells is associated with inhibition of rRNA processing and (2',5') oligo (A) activation of RNase L. Biochem Biophys Res Commun. 1988 Mar 30;151(3):1180–1187. doi: 10.1016/s0006-291x(88)80490-x. [DOI] [PubMed] [Google Scholar]
  10. Chardès T., Buzoni-Gatel D., Lepage A., Bernard F., Bout D. Toxoplasma gondii oral infection induces specific cytotoxic CD8 alpha/beta+ Thy-1+ gut intraepithelial lymphocytes, lytic for parasite-infected enterocytes. J Immunol. 1994 Nov 15;153(10):4596–4603. [PubMed] [Google Scholar]
  11. Cludts I., Cleuter Y., Kettmann R., Burny A., Droogmans L. Cloning and characterization of the tandemly arranged bovine lymphotoxin and tumour necrosis factor-alpha genes. Cytokine. 1993 Jul;5(4):336–341. doi: 10.1016/1043-4666(93)90065-d. [DOI] [PubMed] [Google Scholar]
  12. Current W. L. Cryptosporidiosis. J Am Vet Med Assoc. 1985 Dec 15;187(12):1334–1338. [PubMed] [Google Scholar]
  13. D'Antonio R. G., Winn R. E., Taylor J. P., Gustafson T. L., Current W. L., Rhodes M. M., Gary G. W., Jr, Zajac R. A. A waterborne outbreak of cryptosporidiosis in normal hosts. Ann Intern Med. 1985 Dec;103(6 ):886–888. doi: 10.7326/0003-4819-103-6-886. [DOI] [PubMed] [Google Scholar]
  14. Davis W. C., MacHugh N. D., Park Y. H., Hamilton M. J., Wyatt C. R. Identification of a monoclonal antibody reactive with the bovine orthologue of CD3 (BoCD3). Vet Immunol Immunopathol. 1993 Nov;39(1-3):85–91. doi: 10.1016/0165-2427(93)90167-3. [DOI] [PubMed] [Google Scholar]
  15. Fayer R., Ungar B. L. Cryptosporidium spp. and cryptosporidiosis. Microbiol Rev. 1986 Dec;50(4):458–483. doi: 10.1128/mr.50.4.458-483.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gallaher M. M., Herndon J. L., Nims L. J., Sterling C. R., Grabowski D. J., Hull H. F. Cryptosporidiosis and surface water. Am J Public Health. 1989 Jan;79(1):39–42. doi: 10.2105/ajph.79.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Griebel P. J., Davis W. C., Reynolds J. D. An analysis of the growth and differentiation of B cells isolated from follicles of the ileal Peyer's patch of sheep. Immunology. 1992 Apr;75(4):601–607. [PMC free article] [PubMed] [Google Scholar]
  18. Guy-Grand D., Vassalli P. Gut intraepithelial T lymphocytes. Curr Opin Immunol. 1993 Apr;5(2):247–252. doi: 10.1016/0952-7915(93)90012-h. [DOI] [PubMed] [Google Scholar]
  19. Halpern M. D., Kurlander R. J., Pisetsky D. S. Bacterial DNA induces murine interferon-gamma production by stimulation of interleukin-12 and tumor necrosis factor-alpha. Cell Immunol. 1996 Jan 10;167(1):72–78. doi: 10.1006/cimm.1996.0009. [DOI] [PubMed] [Google Scholar]
  20. Hash S. M., Brown W. C., Rice-Ficht A. C. Characterization of a cDNA encoding bovine interleukin 10: kinetics of expression in bovine lymphocytes. Gene. 1994 Feb 25;139(2):257–261. doi: 10.1016/0378-1119(94)90766-8. [DOI] [PubMed] [Google Scholar]
  21. Hayes E. B., Matte T. D., O'Brien T. R., McKinley T. W., Logsdon G. S., Rose J. B., Ungar B. L., Word D. M., Pinsky P. F., Cummings M. L. Large community outbreak of cryptosporidiosis due to contamination of a filtered public water supply. N Engl J Med. 1989 May 25;320(21):1372–1376. doi: 10.1056/NEJM198905253202103. [DOI] [PubMed] [Google Scholar]
  22. Heussler V. T., Eichhorn M., Dobbelaere D. A. Cloning of a full-length cDNA encoding bovine interleukin 4 by the polymerase chain reaction. Gene. 1992 May 15;114(2):273–278. doi: 10.1016/0378-1119(92)90587-f. [DOI] [PubMed] [Google Scholar]
  23. Horie K., Hirasawa A., Masuda K., Tsujimoto G. Identification of alpha 1C-adrenergic receptor mRNA in bovine retinal pigment epithelium. Invest Ophthalmol Vis Sci. 1993 Aug;34(9):2769–2775. [PubMed] [Google Scholar]
  24. Howard C. J., Morrison W. I., Bensaid A., Davis W., Eskra L., Gerdes J., Hadam M., Hurley D., Leibold W., Letesson J. J. Summary of workshop findings for leukocyte antigens of cattle. Vet Immunol Immunopathol. 1991 Jan;27(1-3):21–27. doi: 10.1016/0165-2427(91)90072-k. [DOI] [PubMed] [Google Scholar]
  25. Lefrançois L. Intraepithelial lymphocytes of the intestinal mucosa: curiouser and curiouser. Semin Immunol. 1991 Mar;3(2):99–108. [PubMed] [Google Scholar]
  26. MacHugh N. D., Taracha E. L., Toye P. G. Reactivity of workshop antibodies on L cell and COS cell transfectants expressing bovine CD antigens. Vet Immunol Immunopathol. 1993 Nov;39(1-3):61–67. doi: 10.1016/0165-2427(93)90164-y. [DOI] [PubMed] [Google Scholar]
  27. McAnulty J. M., Fleming D. W., Gonzalez A. H. A community-wide outbreak of cryptosporidiosis associated with swimming at a wave pool. JAMA. 1994 Nov 23;272(20):1597–1600. [PubMed] [Google Scholar]
  28. Mowat A. M. Antibodies to IFN-gamma prevent immunologically mediated intestinal damage in murine graft-versus-host reaction. Immunology. 1989 Sep;68(1):18–23. [PMC free article] [PubMed] [Google Scholar]
  29. Perryman L. E., Bjorneby J. M. Immunotherapy of cryptosporidiosis in immunodeficient animal models. J Protozool. 1991 Nov-Dec;38(6):98S–100S. [PubMed] [Google Scholar]
  30. Perryman L. E., Mason P. H., Chrisp C. E. Effect of spleen cell populations on resolution of Cryptosporidium parvum infection in SCID mice. Infect Immun. 1994 Apr;62(4):1474–1477. doi: 10.1128/iai.62.4.1474-1477.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Rodriguez P., Heyman M., Candalh C., Blaton M. A., Bouchaud C. Tumour necrosis factor-alpha induces morphological and functional alterations of intestinal HT29 cl.19A cell monolayers. Cytokine. 1995 Jul;7(5):441–448. doi: 10.1006/cyto.1995.0060. [DOI] [PubMed] [Google Scholar]
  32. Schiller J. H., Bittner G., Storer B., Willson J. K. Synergistic antitumor effects of tumor necrosis factor and gamma-interferon on human colon carcinoma cell lines. Cancer Res. 1987 Jun 1;47(11):2809–2813. [PubMed] [Google Scholar]
  33. Schwartz L. M., Osborne B. A. Programmed cell death, apoptosis and killer genes. Immunol Today. 1993 Dec;14(12):582–590. doi: 10.1016/0167-5699(93)90197-S. [DOI] [PubMed] [Google Scholar]
  34. Sydora B. C., Mixter P. F., Holcombe H. R., Eghtesady P., Williams K., Amaral M. C., Nel A., Kronenberg M. Intestinal intraepithelial lymphocytes are activated and cytolytic but do not proliferate as well as other T cells in response to mitogenic signals. J Immunol. 1993 Mar 15;150(6):2179–2191. [PubMed] [Google Scholar]
  35. Tzipori S. Cryptosporidiosis in animals and humans. Microbiol Rev. 1983 Mar;47(1):84–96. doi: 10.1128/mr.47.1.84-96.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tzipori S. Cryptosporidiosis in perspective. Adv Parasitol. 1988;27:63–129. doi: 10.1016/S0065-308X(08)60353-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ungar B. L., Burris J. A., Quinn C. A., Finkelman F. D. New mouse models for chronic Cryptosporidium infection in immunodeficient hosts. Infect Immun. 1990 Apr;58(4):961–969. doi: 10.1128/iai.58.4.961-969.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ungar B. L., Kao T. C., Burris J. A., Finkelman F. D. Cryptosporidium infection in an adult mouse model. Independent roles for IFN-gamma and CD4+ T lymphocytes in protective immunity. J Immunol. 1991 Aug 1;147(3):1014–1022. [PubMed] [Google Scholar]
  39. Whitmire W. M., Harp J. A. Characterization of bovine cellular and serum antibody responses during infection by Cryptosporidium parvum. Infect Immun. 1991 Mar;59(3):990–995. doi: 10.1128/iai.59.3.990-995.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wyatt C. R., Brackett E. J., Perryman L. E., Davis W. C. Identification of gamma delta T lymphocyte subsets that populate calf ileal mucosa after birth. Vet Immunol Immunopathol. 1996 Jun 15;52(1-2):91–103. doi: 10.1016/0165-2427(95)05535-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Wyatt C. R., Davis W. C., McGuire T. C., Perryman L. E. T lymphocyte development in horses. I. Characterization of monoclonal antibodies identifying three stages of T lymphocyte differentiation. Vet Immunol Immunopathol. 1988 Feb;18(1):3–18. doi: 10.1016/0165-2427(88)90032-3. [DOI] [PubMed] [Google Scholar]
  42. Wyatt C. R., Madruga C., Cluff C., Parish S., Hamilton M. J., Goff W., Davis W. C. Differential distribution of gamma delta T-cell receptor lymphocyte subpopulations in blood and spleen of young and adult cattle. Vet Immunol Immunopathol. 1994 Mar;40(3):187–199. doi: 10.1016/0165-2427(94)90019-1. [DOI] [PubMed] [Google Scholar]

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