Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1996 Nov;64(11):4606–4611. doi: 10.1128/iai.64.11.4606-4611.1996

Generation of gamma interferon responses in murine Peyer's patches following oral immunization.

A George 1
PMCID: PMC174420  PMID: 8890214

Abstract

To date, oral immunizations have been shown to generate only Th2 responses in murine Peyer's patches (PP), raising the possibility that T cells present in PP may be capable of mounting only Th2 responses or that the microenvironment of PP does not favor the generation of Th1 cells. However, it is also possible that antigens that can generate Th1 responses have not yet been used for oral immunizations. This study shows that T cells in PP of mice immunized orally with live Salmonella typhimurium secrete large amounts of gamma interferon (IFN-gamma) when they are stimulated with bacterial sonicate in vitro. Moreover, oral challenge of mice with live bacteria 4 months after immunization elicits a secondary IFN-gamma response in PP and mesenteric lymph nodes. Parenteral immunization does not generate an IFN-gamma T-cell response in PP, and parenteral challenge of orally immunized mice does not elicit a secondary response in PP. However, oral challenge of intraperitoneally immunized mice elicits a secondary IFN-gamma response in PP and mesenteric lymph nodes, and intraperitoneal challenge of orally immunized mice elicits a secondary response in the spleen. The data suggest that memory T cells recirculate between mucosal and nonmucosal compartments and that they may be recruited to the site of antigenic challenge.

Full Text

The Full Text of this article is available as a PDF (252.8 KB).

Selected References

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

  1. Alpuche Aranda C. M., Swanson J. A., Loomis W. P., Miller S. I. Salmonella typhimurium activates virulence gene transcription within acidified macrophage phagosomes. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10079–10083. doi: 10.1073/pnas.89.21.10079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carter P. B., Collins F. M. The route of enteric infection in normal mice. J Exp Med. 1974 May 1;139(5):1189–1203. doi: 10.1084/jem.139.5.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cebra J. J., Gearhart P. J., Kamat R., Robertson S. M., Tseng J. Origin and differentiation of lymphocytes involved in the secretory IgA responses. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):201–215. doi: 10.1101/sqb.1977.041.01.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clark M. A., Jepson M. A., Simmons N. L., Hirst B. H. Preferential interaction of Salmonella typhimurium with mouse Peyer's patch M cells. Res Microbiol. 1994 Sep;145(7):543–552. doi: 10.1016/0923-2508(94)90031-0. [DOI] [PubMed] [Google Scholar]
  5. Degré M., Bukholm G., Czarniecki C. W. In vitro treatment of HEp-2 cells with human tumor necrosis factor-alpha and human interferons reduces invasiveness of Salmonella typhimurium. J Biol Regul Homeost Agents. 1989 Jan-Mar;3(1):1–7. [PubMed] [Google Scholar]
  6. Dunkley M. L., Husband A. J. Distribution and functional characteristics of antigen-specific helper T cells arising after Peyer's patch immunization. Immunology. 1987 Aug;61(4):475–482. [PMC free article] [PubMed] [Google Scholar]
  7. Else K. J., Hültner L., Grencis R. K. Cellular immune responses to the murine nematode parasite Trichuris muris. II. Differential induction of TH-cell subsets in resistant versus susceptible mice. Immunology. 1992 Feb;75(2):232–237. [PMC free article] [PubMed] [Google Scholar]
  8. Gautreaux M. D., Deitch E. A., Berg R. D. T lymphocytes in host defense against bacterial translocation from the gastrointestinal tract. Infect Immun. 1994 Jul;62(7):2874–2884. doi: 10.1128/iai.62.7.2874-2884.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hohmann A. W., Schmidt G., Rowley D. Intestinal colonization and virulence of Salmonella in mice. Infect Immun. 1978 Dec;22(3):763–770. doi: 10.1128/iai.22.3.763-770.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hsieh C. S., Macatonia S. E., O'Garra A., Murphy K. M. Pathogen-induced Th1 phenotype development in CD4+ alpha beta-TCR transgenic T cells is macrophage dependent. Int Immunol. 1993 Apr;5(4):371–382. doi: 10.1093/intimm/5.4.371. [DOI] [PubMed] [Google Scholar]
  11. Hsieh C. S., Macatonia S. E., Tripp C. S., Wolf S. F., O'Garra A., Murphy K. M. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. doi: 10.1126/science.8097338. [DOI] [PubMed] [Google Scholar]
  12. Kohbata S., Yokoyama H., Yabuuchi E. Cytopathogenic effect of Salmonella typhi GIFU 10007 on M cells of murine ileal Peyer's patches in ligated ileal loops: an ultrastructural study. Microbiol Immunol. 1986;30(12):1225–1237. doi: 10.1111/j.1348-0421.1986.tb03055.x. [DOI] [PubMed] [Google Scholar]
  13. Kramer D. R., Cebra J. J. Early appearance of "natural" mucosal IgA responses and germinal centers in suckling mice developing in the absence of maternal antibodies. J Immunol. 1995 Mar 1;154(5):2051–2062. [PubMed] [Google Scholar]
  14. Lee I. S., Slonczewski J. L., Foster J. W. A low-pH-inducible, stationary-phase acid tolerance response in Salmonella typhimurium. J Bacteriol. 1994 Mar;176(5):1422–1426. doi: 10.1128/jb.176.5.1422-1426.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Marinaro M., Staats H. F., Hiroi T., Jackson R. J., Coste M., Boyaka P. N., Okahashi N., Yamamoto M., Kiyono H., Bluethmann H. Mucosal adjuvant effect of cholera toxin in mice results from induction of T helper 2 (Th2) cells and IL-4. J Immunol. 1995 Nov 15;155(10):4621–4629. [PubMed] [Google Scholar]
  16. McDermott M. R., Bienenstock J. Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory, and genital tissues. J Immunol. 1979 May;122(5):1892–1898. [PubMed] [Google Scholar]
  17. McWilliams M., Phillips-Quagliata J. M., Lamm M. E. Mesenteric lymph node B lymphoblasts which home to the small intestine are precommitted to IgA synthesis. J Exp Med. 1977 Apr 1;145(4):866–875. doi: 10.1084/jem.145.4.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Muotiala A., Mäkelä P. H. The role of IFN-gamma in murine Salmonella typhimurium infection. Microb Pathog. 1990 Feb;8(2):135–141. doi: 10.1016/0882-4010(90)90077-4. [DOI] [PubMed] [Google Scholar]
  19. Nauciel C., Espinasse-Maes F. Role of gamma interferon and tumor necrosis factor alpha in resistance to Salmonella typhimurium infection. Infect Immun. 1992 Feb;60(2):450–454. doi: 10.1128/iai.60.2.450-454.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Phillips-Quagliata J. M., Roux M. E., Arny M., Kelly-Hatfield P., McWilliams M., Lamm M. E. Migration and regulation of B-cells in the mucosal immune system. Ann N Y Acad Sci. 1983 Jun 30;409:194–203. doi: 10.1111/j.1749-6632.1983.tb26869.x. [DOI] [PubMed] [Google Scholar]
  21. Ramarathinam L., Niesel D. W., Klimpel G. R. Salmonella typhimurium induces IFN-gamma production in murine splenocytes. Role of natural killer cells and macrophages. J Immunol. 1993 May 1;150(9):3973–3981. [PubMed] [Google Scholar]
  22. Ramarathinam L., Shaban R. A., Niesel D. W., Klimpel G. R. Interferon gamma (IFN-gamma) production by gut-associated lymphoid tissue and spleen following oral Salmonella typhimurium challenge. Microb Pathog. 1991 Nov;11(5):347–356. doi: 10.1016/0882-4010(91)90020-b. [DOI] [PubMed] [Google Scholar]
  23. Scharton T. M., Scott P. Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. J Exp Med. 1993 Aug 1;178(2):567–577. doi: 10.1084/jem.178.2.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Scott P., Natovitz P., Coffman R. L., Pearce E., Sher A. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. J Exp Med. 1988 Nov 1;168(5):1675–1684. doi: 10.1084/jem.168.5.1675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Soncini F. C., Véscovi E. G., Groisman E. A. Transcriptional autoregulation of the Salmonella typhimurium phoPQ operon. J Bacteriol. 1995 Aug;177(15):4364–4371. doi: 10.1128/jb.177.15.4364-4371.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Swain S. L. Significance of Lyt phenotypes: Lyt2 antibodies block activities of T cells that recognize class 1 major histocompatibility complex antigens regardless of their function. Proc Natl Acad Sci U S A. 1981 Nov;78(11):7101–7105. doi: 10.1073/pnas.78.11.7101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Taylor-Robinson A. W., Phillips R. S., Severn A., Moncada S., Liew F. Y. The role of TH1 and TH2 cells in a rodent malaria infection. Science. 1993 Jun 25;260(5116):1931–1934. doi: 10.1126/science.8100366. [DOI] [PubMed] [Google Scholar]
  28. Thatte J., Rath S., Bal V. Immunization with live versus killed Salmonella typhimurium leads to the generation of an IFN-gamma-dominant versus an IL-4-dominant immune response. Int Immunol. 1993 Nov;5(11):1431–1436. doi: 10.1093/intimm/5.11.1431. [DOI] [PubMed] [Google Scholar]
  29. Tonkonogy S. L., Swain S. L. Distinct lymphokine production by CD4+ T cells isolated from mucosal and systemic lymphoid organs. Immunology. 1993 Dec;80(4):574–580. [PMC free article] [PubMed] [Google Scholar]
  30. Wilde D. B., Marrack P., Kappler J., Dialynas D. P., Fitch F. W. Evidence implicating L3T4 in class II MHC antigen reactivity; monoclonal antibody GK1.5 (anti-L3T4a) blocks class II MHC antigen-specific proliferation, release of lymphokines, and binding by cloned murine helper T lymphocyte lines. J Immunol. 1983 Nov;131(5):2178–2183. [PubMed] [Google Scholar]
  31. Wilson A. D., Bailey M., Williams N. A., Stokes C. R. The in vitro production of cytokines by mucosal lymphocytes immunized by oral administration of keyhole limpet hemocyanin using cholera toxin as an adjuvant. Eur J Immunol. 1991 Oct;21(10):2333–2339. doi: 10.1002/eji.1830211007. [DOI] [PubMed] [Google Scholar]
  32. Xu-Amano J., Aicher W. K., Taguchi T., Kiyono H., McGhee J. R. Selective induction of Th2 cells in murine Peyer's patches by oral immunization. Int Immunol. 1992 Apr;4(4):433–445. doi: 10.1093/intimm/4.4.433. [DOI] [PubMed] [Google Scholar]
  33. Xu-Amano J., Kiyono H., Jackson R. J., Staats H. F., Fujihashi K., Burrows P. D., Elson C. O., Pillai S., McGhee J. R. Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues. J Exp Med. 1993 Oct 1;178(4):1309–1320. doi: 10.1084/jem.178.4.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES