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. 1990 Jan 1;171(1):159–171. doi: 10.1084/jem.171.1.159

Tumor necrosis factor alpha maintains the viability of murine epidermal Langerhans cells in culture, but in contrast to granulocyte/macrophage colony-stimulating factor, without inducing their functional maturation

PMCID: PMC2187649  PMID: 2404080

Abstract

Freshly isolated murine epidermal Langerhans cells (LC) are weak stimulators of resting T cells but increase their stimulatory capacity 10-30-fold upon 2-3 d of culture together with other epidermal cells. This maturation of LC is mediated by two keratinocyte products. Granulocyte/macrophage colony-stimulating factor (GM-CSF) maintains viability and increases function. IL-1 alone does not keep LC alive, but when combined with GM-CSF further enhances their stimulatory activity. We have now searched for a cytokine that would keep LC in a viable, but functionally immature state. When LC (enriched to greater than 75%) were cultured in the presence of GM-CSF (2 ng/ml) or murine (TNF-alpha) (plateau effect at 62 U/ml), the recovery of viable LC after 72 h was identical. The LC cultured in murine TNF-alpha, however, were 10-30 times less active in stimulating resting T cells. A series of experiments demonstrated that this phenomenon was not due to the induction of insufficient amounts of GM-CSF, the induction of a suppressor factor, or a toxic effect of TNF-alpha. Interestingly, the observed TNF-alpha activity exhibited a species preference, as human TNF-alpha was not active at comparable doses. We have observed an unexpected effect of TNF-alpha on LC in vitro. Though we found that freshly prepared epidermal cells express TNF-alpha mRNA, further studies are needed to establish whether TNF-alpha plays a role in vivo by keeping resident LC in a viable, but functionally immature state.

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Selected References

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  1. Beutler B., Cerami A. The biology of cachectin/TNF--a primary mediator of the host response. Annu Rev Immunol. 1989;7:625–655. doi: 10.1146/annurev.iy.07.040189.003205. [DOI] [PubMed] [Google Scholar]
  2. Chen H. D., Ma C. L., Yuan J. T., Wang Y. K., Silvers W. K. Occurrence of donor Langerhans cells in mouse and rat chimeras and their replacement in skin grafts. J Invest Dermatol. 1986 Jun;86(6):630–633. doi: 10.1111/1523-1747.ep12275627. [DOI] [PubMed] [Google Scholar]
  3. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  4. Cleveland D. W., Lopata M. A., MacDonald R. J., Cowan N. J., Rutter W. J., Kirschner M. W. Number and evolutionary conservation of alpha- and beta-tubulin and cytoplasmic beta- and gamma-actin genes using specific cloned cDNA probes. Cell. 1980 May;20(1):95–105. doi: 10.1016/0092-8674(80)90238-x. [DOI] [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  6. Gay D. A., Yen T. J., Lau J. T., Cleveland D. W. Sequences that confer beta-tubulin autoregulation through modulated mRNA stability reside within exon 1 of a beta-tubulin mRNA. Cell. 1987 Aug 28;50(5):671–679. doi: 10.1016/0092-8674(87)90325-4. [DOI] [PubMed] [Google Scholar]
  7. Gough N. M., Metcalf D., Gough J., Grail D., Dunn A. R. Structure and expression of the mRNA for murine granulocyte-macrophage colony stimulating factor. EMBO J. 1985 Mar;4(3):645–653. doi: 10.1002/j.1460-2075.1985.tb03678.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hauser C., Katz S. I. Activation and expansion of hapten- and protein-specific T helper cells from nonsensitized mice. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5625–5628. doi: 10.1073/pnas.85.15.5625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hauser C., Snapper C. M., Ohara J., Paul W. E., Katz S. I. T helper cells grown with hapten-modified cultured Langerhans' cells produce interleukin 4 and stimulate IgE production by B cells. Eur J Immunol. 1989 Feb;19(2):245–251. doi: 10.1002/eji.1830190205. [DOI] [PubMed] [Google Scholar]
  10. Heufler C., Koch F., Schuler G. Granulocyte/macrophage colony-stimulating factor and interleukin 1 mediate the maturation of murine epidermal Langerhans cells into potent immunostimulatory dendritic cells. J Exp Med. 1988 Feb 1;167(2):700–705. doi: 10.1084/jem.167.2.700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Inaba K., Romani N., Steinman R. M. An antigen-independent contact mechanism as an early step in T cell-proliferative responses to dendritic cells. J Exp Med. 1989 Aug 1;170(2):527–542. doi: 10.1084/jem.170.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Inaba K., Schuler G., Witmer M. D., Valinksy J., Atassi B., Steinman R. M. Immunologic properties of purified epidermal Langerhans cells. Distinct requirements for stimulation of unprimed and sensitized T lymphocytes. J Exp Med. 1986 Aug 1;164(2):605–613. doi: 10.1084/jem.164.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kriegler M., Perez C., DeFay K., Albert I., Lu S. D. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell. 1988 Apr 8;53(1):45–53. doi: 10.1016/0092-8674(88)90486-2. [DOI] [PubMed] [Google Scholar]
  14. Krueger G. G., Daynes R. A., Emam M. Biology of Langerhans cells: selective migration of Langerhans cells into allogeneic and xenogeneic grafts on nude mice. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1650–1654. doi: 10.1073/pnas.80.6.1650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lomedico P. T., Gubler U., Hellmann C. P., Dukovich M., Giri J. G., Pan Y. C., Collier K., Semionow R., Chua A. O., Mizel S. B. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. 1984 Nov 29-Dec 5Nature. 312(5993):458–462. doi: 10.1038/312458a0. [DOI] [PubMed] [Google Scholar]
  16. Mochizuki D. Y., Eisenman J. R., Conlon P. J., Park L. S., Urdal D. L. Development and characterization of antiserum to murine granulocyte-macrophage colony-stimulating factor. J Immunol. 1986 May 15;136(10):3706–3709. [PubMed] [Google Scholar]
  17. Oxholm A., Oxholm P., Staberg B., Bendtzen K. Immunohistological detection of interleukin I-like molecules and tumour necrosis factor in human epidermis before and after UVB-irradiation in vivo. Br J Dermatol. 1988 Mar;118(3):369–376. doi: 10.1111/j.1365-2133.1988.tb02430.x. [DOI] [PubMed] [Google Scholar]
  18. Ranges G. E., Bombara M. P., Aiyer R. A., Rice G. G., Palladino M. A., Jr Tumor necrosis factor-alpha as a proliferative signal for an IL-2-dependent T cell line: strict species specificity of action. J Immunol. 1989 Feb 15;142(4):1203–1208. [PubMed] [Google Scholar]
  19. Ranges G. E., Zlotnik A., Espevik T., Dinarello C. A., Cerami A., Palladino M. A., Jr Tumor necrosis factor alpha/cachectin is a growth factor for thymocytes. Synergistic interactions with other cytokines. J Exp Med. 1988 Apr 1;167(4):1472–1478. doi: 10.1084/jem.167.4.1472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Romani N., Koide S., Crowley M., Witmer-Pack M., Livingstone A. M., Fathman C. G., Inaba K., Steinman R. M. Presentation of exogenous protein antigens by dendritic cells to T cell clones. Intact protein is presented best by immature, epidermal Langerhans cells. J Exp Med. 1989 Mar 1;169(3):1169–1178. doi: 10.1084/jem.169.3.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schuler G., Steinman R. M. Murine epidermal Langerhans cells mature into potent immunostimulatory dendritic cells in vitro. J Exp Med. 1985 Mar 1;161(3):526–546. doi: 10.1084/jem.161.3.526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sherry B., Cerami A. Cachectin/tumor necrosis factor exerts endocrine, paracrine, and autocrine control of inflammatory responses. J Cell Biol. 1988 Oct;107(4):1269–1277. doi: 10.1083/jcb.107.4.1269. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Shimada S., Caughman S. W., Sharrow S. O., Stephany D., Katz S. I. Enhanced antigen-presenting capacity of cultured Langerhans' cells is associated with markedly increased expression of Ia antigen. J Immunol. 1987 Oct 15;139(8):2551–2555. [PubMed] [Google Scholar]
  24. Steinman R. M., Nussenzweig M. C. Dendritic cells: features and functions. Immunol Rev. 1980;53:127–147. doi: 10.1111/j.1600-065x.1980.tb01042.x. [DOI] [PubMed] [Google Scholar]
  25. Steinman R., Inaba K. Immunogenicity: role of dendritic cells. Bioessays. 1989 May;10(5):145–152. doi: 10.1002/bies.950100503. [DOI] [PubMed] [Google Scholar]
  26. Tamaki K., Katz S. I. Ontogeny of Langerhans cells. J Invest Dermatol. 1980 Jul;75(1):12–13. doi: 10.1111/1523-1747.ep12521037. [DOI] [PubMed] [Google Scholar]
  27. Tschachler E., Schuler G., Hutterer J., Leibl H., Wolff K., Stingl G. Expression of Thy-1 antigen by murine epidermal cells. J Invest Dermatol. 1983 Sep;81(3):282–285. doi: 10.1111/1523-1747.ep12518326. [DOI] [PubMed] [Google Scholar]
  28. Witmer-Pack M. D., Olivier W., Valinsky J., Schuler G., Steinman R. M. Granulocyte/macrophage colony-stimulating factor is essential for the viability and function of cultured murine epidermal Langerhans cells. J Exp Med. 1987 Nov 1;166(5):1484–1498. doi: 10.1084/jem.166.5.1484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Witmer-Pack M. D., Valinsky J., Olivier W., Steinman R. M. Quantitation of surface antigens on cultured murine epidermal Langerhans cells: rapid and selective increase in the level of surface MHC products. J Invest Dermatol. 1988 Mar;90(3):387–394. doi: 10.1111/1523-1747.ep12456460. [DOI] [PubMed] [Google Scholar]

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