Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Jul;76(1):254–260. doi: 10.1172/JCI111955

Human dermal fibroblasts present tetanus toxoid antigen to antigen-specific T cell clones.

D T Umetsu, J S Pober, H H Jabara, W Fiers, E J Yunis, S J Burakoff, C S Reiss, R S Geha
PMCID: PMC423759  PMID: 3160726

Abstract

Cultured human dermal fibroblasts treated with immune interferon express HLA-DR antigens. We report here that DR-positive fibroblasts present tetanus toxoid (TT) to autologous TT-specific monoclonal helper T cells vigorously depleted of monocytes by passage over Sephadex G10 columns followed by treatment with the monoclonal antibodies (mAb) OKM1 and Leu M1 plus complement. The extent of T cell proliferation in response to TT presented by DR-positive fibroblasts was similar to that elicited using monocytes as antigen-presenting cells. The proliferative response was TT dependent, antigen specific, depended upon DR expression by fibroblasts, appeared MHC restricted, and was completely blocked by mouse mAb to HLA-DR but not by mAb to HLA-A,B, or DQ. DR-positive fibroblasts pulsed with TT were similarly effective in antigen presentation. In summary, immune interferon-stimulated human dermal fibroblasts can substitute for classical antigen-presenting cells in antigen-specific proliferative responses. Since fibroblasts are a ubiquitous cell type in the body, they may play a significant role in the immunobiology of the host.

Full text

PDF
254

Selected References

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

  1. Barnstable C. J., Bodmer W. F., Brown G., Galfre G., Milstein C., Williams A. F., Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens-new tools for genetic analysis. Cell. 1978 May;14(1):9–20. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  2. Breard J., Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol. 1980 Apr;124(4):1943–1948. [PubMed] [Google Scholar]
  3. Chesnut R. W., Colon S. M., Grey H. M. Antigen presentation by normal B cells, B cell tumors, and macrophages: functional and biochemical comparison. J Immunol. 1982 Apr;128(4):1764–1768. [PubMed] [Google Scholar]
  4. Chu E. T., Lareau M., Rosenwasser L. J., Dinarello C. A., Geha R. S. Antigen presentation by EBV-B cells to resting and activated T cells: role of interleukin 1. J Immunol. 1985 Mar;134(3):1676–1681. [PubMed] [Google Scholar]
  5. Collins T., Korman A. J., Wake C. T., Boss J. M., Kappes D. J., Fiers W., Ault K. A., Gimbrone M. A., Jr, Strominger J. L., Pober J. S. Immune interferon activates multiple class II major histocompatibility complex genes and the associated invariant chain gene in human endothelial cells and dermal fibroblasts. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4917–4921. doi: 10.1073/pnas.81.15.4917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fontana A., Fierz W., Wekerle H. Astrocytes present myelin basic protein to encephalitogenic T-cell lines. Nature. 1984 Jan 19;307(5948):273–276. doi: 10.1038/307273a0. [DOI] [PubMed] [Google Scholar]
  7. Glimcher L. H., Kim K. J., Green I., Paul W. E. Ia antigen-bearing B cell tumor lines can present protein antigen and alloantigen in a major histocompatibility complex-restricted fashion to antigen-reactive T cells. J Exp Med. 1982 Feb 1;155(2):445–459. doi: 10.1084/jem.155.2.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Habu S., Raff M. C. Accessory cell dependence of lectin-induced proliferation of mouse T lymphocytes. Eur J Immunol. 1977 Jul;7(7):451–457. doi: 10.1002/eji.1830070710. [DOI] [PubMed] [Google Scholar]
  9. Hanjan S. N., Kearney J. F., Cooper M. D. A monoclonal antibody (MMA) that identifies a differentiation antigen on human myelomonocytic cells. Clin Immunol Immunopathol. 1982 May;23(2):172–188. doi: 10.1016/0090-1229(82)90106-4. [DOI] [PubMed] [Google Scholar]
  10. Hirschberg H., Braathen L. R., Thorsby E. Antigen presentation by vascular endothelial cells and epidermal Langerhans cells: the role of HLA-DR. Immunol Rev. 1982;66:57–77. doi: 10.1111/j.1600-065x.1982.tb00434.x. [DOI] [PubMed] [Google Scholar]
  11. Issekutz T., Chu E., Geha R. S. Antigen presentation by human B cells: T cell proliferation induced by Epstein Barr virus B lymphoblastoid cells. J Immunol. 1982 Oct;129(4):1446–1450. [PubMed] [Google Scholar]
  12. Katz D. H., Unanue E. R. Critical role of determinant presentation in the induction of specific responses in immunocompetent lymphocytes. J Exp Med. 1973 Apr 1;137(4):967–990. doi: 10.1084/jem.137.4.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Klein J., Nagy Z. A. Mhc restriction and Ir genes. Adv Cancer Res. 1982;37:233–317. doi: 10.1016/s0065-230x(08)60885-4. [DOI] [PubMed] [Google Scholar]
  14. Lamb J. R., Eckels D. D., Lake P., Johnson A. H., Hartzman R. J., Woody J. N. Antigen-specific human T lymphocyte clones: induction, antigen specificity, and MHC restriction of influenza virus-immune clones. J Immunol. 1982 Jan;128(1):233–238. [PubMed] [Google Scholar]
  15. Lipsky P. E., Ellner J. J., Rosenthal A. L. Phytohemagglutinin-induced proliferation of guinea pig thymus-derived lymphocytes. I. Accessory cell dependence. J Immunol. 1976 Mar;116(3):868–875. [PubMed] [Google Scholar]
  16. Ly I. A., Mishell R. I. Separation of mouse spleen cells by passage through columns of sephadex G-10. J Immunol Methods. 1974 Aug;5(3):239–247. doi: 10.1016/0022-1759(74)90108-2. [DOI] [PubMed] [Google Scholar]
  17. Malissen B., Price M. P., Goverman J. M., McMillan M., White J., Kappler J., Marrack P., Pierres A., Pierres M., Hood L. Gene transfer of H-2 class II genes: antigen presentation by mouse fibroblast and hamster B-cell lines. Cell. 1984 Feb;36(2):319–327. doi: 10.1016/0092-8674(84)90225-3. [DOI] [PubMed] [Google Scholar]
  18. Muchmore A. V., Megson M., Decker J. M., Knudsen P., Mann D. L., Broder S. Inhibitory activity of antibodies to human Ia-like determinants: comparison of intact and pepsin-digested antibodies. J Immunol. 1983 Aug;131(2):725–730. [PubMed] [Google Scholar]
  19. Nussenzweig M. C., Steinman R. M., Gutchinov B., Cohn Z. A. Dendritic cells are accessory cells for the development of anti-trinitrophenyl cytotoxic T lymphocytes. J Exp Med. 1980 Oct 1;152(4):1070–1084. doi: 10.1084/jem.152.4.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pober J. S., Collins T., Gimbrone M. A., Jr, Cotran R. S., Gitlin J. D., Fiers W., Clayberger C., Krensky A. M., Burakoff S. J., Reiss C. S. Lymphocytes recognize human vascular endothelial and dermal fibroblast Ia antigens induced by recombinant immune interferon. Nature. 1983 Oct 20;305(5936):726–729. doi: 10.1038/305726a0. [DOI] [PubMed] [Google Scholar]
  21. Pober J. S., Gimbrone M. A., Jr, Cotran R. S., Reiss C. S., Burakoff S. J., Fiers W., Ault K. A. Ia expression by vascular endothelium is inducible by activated T cells and by human gamma interferon. J Exp Med. 1983 Apr 1;157(4):1339–1353. doi: 10.1084/jem.157.4.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Silberberg-Sinakin I., Gigli I., Baer R. L., Thorbecke G. J. Langerhans cells: role in contact hypersensitivity and relationship to lymphoid dendritic cells and to macrophages. Immunol Rev. 1980;53:203–232. doi: 10.1111/j.1600-065x.1980.tb01045.x. [DOI] [PubMed] [Google Scholar]
  23. Steeg P. S., Moore R. N., Johnson H. M., Oppenheim J. J. Regulation of murine macrophage Ia antigen expression by a lymphokine with immune interferon activity. J Exp Med. 1982 Dec 1;156(6):1780–1793. doi: 10.1084/jem.156.6.1780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stingl G., Katz S. I., Clement L., Green I., Shevach E. M. Immunologic functions of Ia-bearing epidermal Langerhans cells. J Immunol. 1978 Nov;121(5):2005–2013. [PubMed] [Google Scholar]
  25. Sunshine G. H., Katz D. R., Feldmann M. Dendritic cells induce T cell proliferation to synthetic antigens under Ir gene control. J Exp Med. 1980 Dec 1;152(6):1817–1822. doi: 10.1084/jem.152.6.1817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Umetsu D. T., Yunis E. J., Matsui Y., Jabara H. H., Geha R. S. HLA-DR-4-associated alloreactivity of an HLA-DR-3-restricted human tetanus toxoid-specific T cell clone: inhibition of both reactivities by an alloantiserum. Eur J Immunol. 1985 Apr;15(4):356–361. doi: 10.1002/eji.1830150410. [DOI] [PubMed] [Google Scholar]
  27. Unanue E. R., Beller D. I., Lu C. Y., Allen P. M. Antigen presentation: comments on its regulation and mechanism. J Immunol. 1984 Jan;132(1):1–5. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES