Abstract
The liver is the major site of clearance and degradation of foreign antigens from the portal circulation. Despite the presence of hepatic accessory cells, antibody responses to orally administered antigens are uncommon. To ascertain if hepatic accessory cells are incapable of stimulating specific subsets of T lymphocytes, freshly isolated hepatic nonparenchymal and splenic cells were cultured with a panel of antigen- specific, H-2-restricted Th1 and Th2 HTL clones. Whereas spleen cells stimulated the proliferation of both Th1 and Th2 clones, hepatic nonparenchymal cells (NPC) stimulated the proliferation of only Th1 and not Th2 clones. Adding rIL-1, rIL-6, and rIL-7, alone or in combination, to the cultures did not result in proliferation of the Th2 clones. Despite the absence of Th2 proliferation, NPC were able to stimulate the secretion of IL-3 and IL-4 by Th2 clones in the presence of antigen. Moreover, adding hepatic NPC did not inhibit spleen cells from stimulating Th2 clones in the presence of antigen. Thus, the inability of liver cells to stimulate the proliferation of Th2 helper T lymphocytes appears to be secondary to an absence of either an unknown accessory cell cofactor or an accessory cell that preferentially presents antigen to Th2 cells. The selective activation of Th1 and not Th2 cells by liver accessory cells may result in suppression of antibody responses to orally administered antigens.
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Selected References
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- Cantor H. M., Dumont A. E. Hepatic suppression of sensitization to antigen absorbed into the portal system. Nature. 1967 Aug 12;215(5102):744–745. doi: 10.1038/215744a0. [DOI] [PubMed] [Google Scholar]
- Gajewski T. F., Fitch F. W. Anti-proliferative effect of IFN-gamma in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J Immunol. 1988 Jun 15;140(12):4245–4252. [PubMed] [Google Scholar]
- Gajewski T. F., Goldwasser E., Fitch F. W. Anti-proliferative effect of IFN-gamma in immune regulation. II. IFN-gamma inhibits the proliferation of murine bone marrow cells stimulated with IL-3, IL-4, or granulocyte-macrophage colony-stimulating factor. J Immunol. 1988 Oct 15;141(8):2635–2642. [PubMed] [Google Scholar]
- Gajewski T. F., Joyce J., Fitch F. W. Antiproliferative effect of IFN-gamma in immune regulation. III. Differential selection of TH1 and TH2 murine helper T lymphocyte clones using recombinant IL-2 and recombinant IFN-gamma. J Immunol. 1989 Jul 1;143(1):15–22. [PubMed] [Google Scholar]
- Garman R. D., Jacobs K. A., Clark S. C., Raulet D. H. B-cell-stimulatory factor 2 (beta 2 interferon) functions as a second signal for interleukin 2 production by mature murine T cells. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7629–7633. doi: 10.1073/pnas.84.21.7629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenbaum L. A., Horowitz J. B., Woods A., Pasqualini T., Reich E. P., Bottomly K. Autocrine growth of CD4+ T cells. Differential effects of IL-1 on helper and inflammatory T cells. J Immunol. 1988 Mar 1;140(5):1555–1560. [PubMed] [Google Scholar]
- Lichtman A. H., Kurt-Jones E. A., Abbas A. K. B-cell stimulatory factor 1 and not interleukin 2 is the autocrine growth factor for some helper T lymphocytes. Proc Natl Acad Sci U S A. 1987 Feb;84(3):824–827. doi: 10.1073/pnas.84.3.824. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morrissey P. J., Goodwin R. G., Nordan R. P., Anderson D., Grabstein K. H., Cosman D., Sims J., Lupton S., Acres B., Reed S. G. Recombinant interleukin 7, pre-B cell growth factor, has costimulatory activity on purified mature T cells. J Exp Med. 1989 Mar 1;169(3):707–716. doi: 10.1084/jem.169.3.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
- Nadler P. I., Klingenstein R. J., Richman L. K., Ahmann G. B. The murine Kupffer cell. II. Accessory cell function in in vitro primary antibody responses, mitogen-induced proliferation, and stimulation of mixed lymphocyte responses. J Immunol. 1980 Dec;125(6):2521–2525. [PubMed] [Google Scholar]
- Quintáns J., Suzuki H., Sosman J. A., Shah P. D. Immunoregulation by T cells. I. Characterization of the IEk-specific Lbd self-reactive T cell clone that helps, suppresses and contrasupresses B cell responses. J Immunol. 1986 Mar 15;136(6):1974–1981. [PubMed] [Google Scholar]
- Rubinstein D., Roska A. K., Lipsky P. E. Antigen presentation by liver sinusoidal lining cells after antigen exposure in vivo. J Immunol. 1987 Mar 1;138(5):1377–1382. [PubMed] [Google Scholar]
- Shah P. D., Rowley D. A., Latta S. L., Magilavy D. B. A comparison of murine hepatic accessory cells and splenic dendritic cells. Cell Immunol. 1989 Feb;118(2):394–405. doi: 10.1016/0008-8749(89)90387-0. [DOI] [PubMed] [Google Scholar]
- Silverman G. A., Peri B. A., Fitch F. W., Rothberg R. M. Enterically induced regulation of systemic immune responses. II. Suppression of proliferating T cells by an Lyt-1+, 2- T effector cell. J Immunol. 1983 Dec;131(6):2656–2661. [PubMed] [Google Scholar]
- Watson J. Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. J Exp Med. 1979 Dec 1;150(6):1510–1519. doi: 10.1084/jem.150.6.1510. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yokoyama A., Evavold B., Dunn D. E., Quintans J. Production of IL-2 and IFN by TH2 clones. Immunol Lett. 1989 May;21(2):119–125. doi: 10.1016/0165-2478(89)90047-3. [DOI] [PubMed] [Google Scholar]