Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1989 Aug;63(8):3507–3512. doi: 10.1128/jvi.63.8.3507-3512.1989

Rotavirus-specific cytotoxic T lymphocytes appear at the intestinal mucosal surface after rotavirus infection.

P A Offit 1, K I Dudzik 1
PMCID: PMC250928  PMID: 2545920

Abstract

The gastrointestinal tract is constantly exposed to a variety of potentially invasive bacteria and viruses. The first line of defense of the host against these pathogens is the intestinal mucosal surface, which consists of epithelial cells, intraepithelial lymphocytes (IELs), mucus, and secretory immunoglobulins. Little is known about the function, memory, or trafficking of IELs after intestinal infection. We found that IELs obtained 6 days after oral inoculation of mice with the intestinal pathogen rotavirus (simian strain RRV) lysed rotavirus-infected target cells; cytotoxic T lymphocytes (CTLs) were responsible for rotavirus-specific cytotoxic activity. Rotavirus-specific cytotoxic activity by IELs was (i) eliminated by treatment with Thy 1.2-specific immunoglobulin M plus complement, (ii) restricted by proteins encoded at the major histocompatibility complex, and (iii) absent in mock-infected animals. Oral inoculation of mice with RRV also induced rotavirus-specific CTLs in splenic and intestinal lymphocytes (mesenteric lymph nodes, Peyer's patch). Parenteral inoculation induced rotavirus-specific CTLs in splenic, intestinal (IELs, mesenteric lymph nodes, Peyer's patch), and nonintestinal lymphocytes (inguinal nodes). Therefore, presentation of rotavirus to the intestinal mucosal surface was not necessary to induce IELs with virus-specific cytotoxic activity. At 4 weeks after oral or parenteral inoculation of mice with RRV, rotavirus-specific CTL precursors appeared among splenic, Peyer's patch, inguinal, and mesenteric node lymphocytes, but not among IELs. IELs with rotavirus-specific cytotoxic activity may be generated from precursors at a site other than the intestinal mucosal surface. Part of the response of the host to enteric infection may include surveillance and lysis of virus-infected villus epithelial cells by IELs.

Full text

PDF
3507

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Black R. E., Merson M. H., Rahman A. S., Yunus M., Alim A. R., Huq I., Yolken R. H., Curlin G. T. A two-year study of bacterial, viral, and parasitic agents associated with diarrhea in rural Bangladesh. J Infect Dis. 1980 Nov;142(5):660–664. doi: 10.1093/infdis/142.5.660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Braciale T. J. Immunologic recognition of influenza virus-infected cells. I. Generation of a virus-strain specific and a cross-reactive subpopulation of cytotoxic T cells in the response to type A influenza viruses of different subtypes. Cell Immunol. 1977 Oct;33(2):423–436. doi: 10.1016/0008-8749(77)90170-8. [DOI] [PubMed] [Google Scholar]
  3. Carlsson B., Zaman S., Mellander L., Jalil F., Hanson L. A. Secretory and serum immunoglobulin class-specific antibodies to poliovirus after vaccination. J Infect Dis. 1985 Dec;152(6):1238–1244. doi: 10.1093/infdis/152.6.1238. [DOI] [PubMed] [Google Scholar]
  4. Cerf-Bensussan N., Guy-Grand D., Griscelli C. Intraepithelial lymphocytes of human gut: isolation, characterisation and study of natural killer activity. Gut. 1985 Jan;26(1):81–88. doi: 10.1136/gut.26.1.81. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dillon S. B., MacDonald T. T. Functional properties of lymphocytes isolated from murine small intestinal epithelium. Immunology. 1984 Jul;52(3):501–509. [PMC free article] [PubMed] [Google Scholar]
  6. Doherty P. C., Zinkernagel R. M. Specific immune lysis of paramyxovirus-infected cells by H-2-compatible thymus-derived lymphocytes. Immunology. 1976 Jul;31(1):27–32. [PMC free article] [PubMed] [Google Scholar]
  7. Ernst P. B., Clark D. A., Rosenthal K. L., Befus A. D., Bienenstock J. Detection and characterization of cytotoxic T lymphocyte precursors in the murine intestinal intraepithelial leukocyte population. J Immunol. 1986 Mar 15;136(6):2121–2126. [PubMed] [Google Scholar]
  8. Fuhrman J. A., Cebra J. J. Special features of the priming process for a secretory IgA response. B cell priming with cholera toxin. J Exp Med. 1981 Mar 1;153(3):534–544. doi: 10.1084/jem.153.3.534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Guy-Grand D., Griscelli C., Vassalli P. The mouse gut T lymphocyte, a novel type of T cell. Nature, origin, and traffic in mice in normal and graft-versus-host conditions. J Exp Med. 1978 Dec 1;148(6):1661–1677. doi: 10.1084/jem.148.6.1661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Issekutz T. B. Characteristics of lymphoblasts appearing in efferent lymph in response to immunization with vaccinia virus. Immunology. 1985 Sep;56(1):23–31. [PMC free article] [PubMed] [Google Scholar]
  11. Jung T. M., Gallatin W. M., Weissman I. L., Dailey M. O. Down-regulation of homing receptors after T cell activation. J Immunol. 1988 Dec 15;141(12):4110–4117. [PubMed] [Google Scholar]
  12. Kapikian A. Z., Kim H. W., Wyatt R. G., Cline W. L., Arrobio J. O., Brandt C. D., Rodriguez W. J., Sack D. A., Chanock R. M., Parrott R. H. Human reovirus-like agent as the major pathogen associated with "winter" gastroenteritis in hospitalized infants and young children. N Engl J Med. 1976 Apr 29;294(18):965–972. doi: 10.1056/NEJM197604292941801. [DOI] [PubMed] [Google Scholar]
  13. Kapikian A. Z., Wyatt R. G., Levine M. M., Yolken R. H., VanKirk D. H., Dolin R., Greenberg H. B., Chanock R. M. Oral administration of human rotavirus to volunteers: induction of illness and correlates of resistance. J Infect Dis. 1983 Jan;147(1):95–106. doi: 10.1093/infdis/147.1.95. [DOI] [PubMed] [Google Scholar]
  14. Klein J. R., Kagnoff M. F. Nonspecific recruitment of cytotoxic effector cells in the intestinal mucosa of antigen-primed mice. J Exp Med. 1984 Dec 1;160(6):1931–1936. doi: 10.1084/jem.160.6.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. London S. D., Rubin D. H., Cebra J. J. Gut mucosal immunization with reovirus serotype 1/L stimulates virus-specific cytotoxic T cell precursors as well as IgA memory cells in Peyer's patches. J Exp Med. 1987 Mar 1;165(3):830–847. doi: 10.1084/jem.165.3.830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Losonsky G. A., Rennels M. B., Lim Y., Krall G., Kapikian A. Z., Levine M. M. Systemic and mucosal immune responses to rhesus rotavirus vaccine MMU 18006. Pediatr Infect Dis J. 1988 Jun;7(6):388–393. doi: 10.1097/00006454-198806000-00004. [DOI] [PubMed] [Google Scholar]
  17. McNabb P. C., Tomasi T. B. Host defense mechanisms at mucosal surfaces. Annu Rev Microbiol. 1981;35:477–496. doi: 10.1146/annurev.mi.35.100181.002401. [DOI] [PubMed] [Google Scholar]
  18. McWilliams M., Lamm M. E., Phillips-Quagliata J. M. Surface and intracellular markers of mouse mesenteric and peripheral lymph node and Peyer's patch cells. J Immunol. 1974 Oct;113(4):1326–1333. [PubMed] [Google Scholar]
  19. Offit P. A., Clark H. F., Blavat G., Greenberg H. B. Reassortant rotaviruses containing structural proteins vp3 and vp7 from different parents induce antibodies protective against each parental serotype. J Virol. 1986 Nov;60(2):491–496. doi: 10.1128/jvi.60.2.491-496.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Offit P. A., Clark H. F., Kornstein M. J., Plotkin S. A. A murine model for oral infection with a primate rotavirus (simian SA11). J Virol. 1984 Jul;51(1):233–236. doi: 10.1128/jvi.51.1.233-236.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Offit P. A., Clark H. F., Plotkin S. A. Response of mice to rotaviruses of bovine or primate origin assessed by radioimmunoassay, radioimmunoprecipitation, and plaque reduction neutralization. Infect Immun. 1983 Oct;42(1):293–300. doi: 10.1128/iai.42.1.293-300.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Offit P. A., Dudzik K. I. Rotavirus-specific cytotoxic T lymphocytes cross-react with target cells infected with different rotavirus serotypes. J Virol. 1988 Jan;62(1):127–131. doi: 10.1128/jvi.62.1.127-131.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Offit P. A., Shaw R. D., Greenberg H. B. Passive protection against rotavirus-induced diarrhea by monoclonal antibodies to surface proteins vp3 and vp7. J Virol. 1986 May;58(2):700–703. doi: 10.1128/jvi.58.2.700-703.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Parrott D. M., Tait C., MacKenzie S., Mowat A. M., Davies M. D., Micklem H. S. Analysis of the effector functions of different populations of mucosal lymphocytes. Ann N Y Acad Sci. 1983 Jun 30;409:307–320. doi: 10.1111/j.1749-6632.1983.tb26879.x. [DOI] [PubMed] [Google Scholar]
  25. Petit A., Ernst P. B., Befus A. D., Clark D. A., Rosenthal K. L., Ishizaka T., Bienenstock J. Murine intestinal intraepithelial lymphocytes I. Relationship of a novel Thy-1-,Lyt-1-,Lyt-2+, granulated subpopulation to natural killer cells and mast cells. Eur J Immunol. 1985 Mar;15(3):211–215. doi: 10.1002/eji.1830150302. [DOI] [PubMed] [Google Scholar]
  26. Röpke C., Everett N. B. Kinetics of intraepithelial lymphocytes in the small intestine of thymus-deprived mice and antigen-deprived mice. Anat Rec. 1976 May;185(1):101–108. doi: 10.1002/ar.1091850110. [DOI] [PubMed] [Google Scholar]
  27. Starkey W. G., Collins J., Wallis T. S., Clarke G. J., Spencer A. J., Haddon S. J., Osborne M. P., Candy D. C., Stephen J. Kinetics, tissue specificity and pathological changes in murine rotavirus infection of mice. J Gen Virol. 1986 Dec;67(Pt 12):2625–2634. doi: 10.1099/0022-1317-67-12-2625. [DOI] [PubMed] [Google Scholar]
  28. Streeter P. R., Berg E. L., Rouse B. T., Bargatze R. F., Butcher E. C. A tissue-specific endothelial cell molecule involved in lymphocyte homing. Nature. 1988 Jan 7;331(6151):41–46. doi: 10.1038/331041a0. [DOI] [PubMed] [Google Scholar]
  29. Totterdell B. M., Banatvala J. E., Chrystie I. L., Ball G., Cubitt W. D. Systemic lymphoproliferative responses to rotavirus. J Med Virol. 1988 May;25(1):37–44. doi: 10.1002/jmv.1890250106. [DOI] [PubMed] [Google Scholar]
  30. Walsh J. A., Warren K. S. Selective primary health care: an interim strategy for disease control in developing countries. N Engl J Med. 1979 Nov 1;301(18):967–974. doi: 10.1056/NEJM197911013011804. [DOI] [PubMed] [Google Scholar]
  31. Wolf J. L., Dambrauskas R., Sharpe A. H., Trier J. S. Adherence to and penetration of the intestinal epithelium by reovirus type 1 in neonatal mice. Gastroenterology. 1987 Jan;92(1):82–91. doi: 10.1016/0016-5085(87)90842-0. [DOI] [PubMed] [Google Scholar]
  32. Zinkernagel R. M., Doherty P. C. MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979;27:51–177. doi: 10.1016/s0065-2776(08)60262-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES