Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1994 May 1;179(5):1689–1694. doi: 10.1084/jem.179.5.1689

Production of the RANTES chemokine in delayed-type hypersensitivity reactions: involvement of macrophages and endothelial cells [published erratum appears in J Exp Med 1994 Aug 1;180(2):775]

PMCID: PMC2191500  PMID: 7513016

Abstract

To understand the selective accumulation of memory T helper lymphocytes and of macrophages in delayed-type hypersensitivity (DTH) granulomas, we studied the in situ production of RANTES, a chemokine initially characterized on the basis of its in vitro chemotactic properties for each of these cell populations. RANTES gene expression was studied by in situ hybridization in 15 human lymph nodes presenting typical DTH lesions related to either sarcoidosis or tuberculosis. A positive signal was detected in all cases. Labeling was specific for the DTH lesions, as very few if any positive cells were detected in the normal residual lymphoid tissue surrounding them or in reactive lymph nodes involved in a B lymphocyte response. RANTES gene expression was associated with the production of the protein, which was detected by immunochemistry in DTH lymph nodes. The morphological characteristics and distribution of positive cells in in situ hybridization and immunochemical experiments indicated that macrophages and endothelial cells, two cell populations not previously reported to produce RANTES, contributed to its production in DTH reactions. The ability of macrophages and endothelial cells to produce RANTES was confirmed by in vitro studies with alveolar macrophages and umbilical vein endothelial cells. In view of the chemotactic properties of RANTES for a limited range of cell populations, these results suggest that RANTES production in DTH granulomas may play a role in the selective accumulation of macrophages and memory T helper lymphocytes characterizing this type of cell-mediated immune reaction, and that macrophages and endothelial cells are involved in this production.

Full Text

The Full Text of this article is available as a PDF (1.5 MB).

Selected References

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

  1. Abehsira-Amar O., Gibert M., Joliy M., Thèze J., Jankovic D. L. IL-4 plays a dominant role in the differential development of Tho into Th1 and Th2 cells. J Immunol. 1992 Jun 15;148(12):3820–3829. [PubMed] [Google Scholar]
  2. Alam R., Stafford S., Forsythe P., Harrison R., Faubion D., Lett-Brown M. A., Grant J. A. RANTES is a chemotactic and activating factor for human eosinophils. J Immunol. 1993 Apr 15;150(8 Pt 1):3442–3448. [PubMed] [Google Scholar]
  3. Arnoldi J., Gerdes J., Flad H. D. Immunohistologic assessment of cytokine production of infiltrating cells in various forms of leprosy. Am J Pathol. 1990 Oct;137(4):749–753. [PMC free article] [PubMed] [Google Scholar]
  4. Barnes P. F., Mistry S. D., Cooper C. L., Pirmez C., Rea T. H., Modlin R. L. Compartmentalization of a CD4+ T lymphocyte subpopulation in tuberculous pleuritis. J Immunol. 1989 Feb 15;142(4):1114–1119. [PubMed] [Google Scholar]
  5. Chensue S. W., Warmington K. S., Berger A. E., Tracey D. E. Immunohistochemical demonstration of interleukin-1 receptor antagonist protein and interleukin-1 in human lymphoid tissue and granulomas. Am J Pathol. 1992 Feb;140(2):269–275. [PMC free article] [PubMed] [Google Scholar]
  6. Dannenberg A. M., Jr Delayed-type hypersensitivity and cell-mediated immunity in the pathogenesis of tuberculosis. Immunol Today. 1991 Jul;12(7):228–233. doi: 10.1016/0167-5699(91)90035-R. [DOI] [PubMed] [Google Scholar]
  7. Devergne O., Emilie D., Peuchmaur M., Crevon M. C., D'Agay M. F., Galanaud P. Production of cytokines in sarcoid lymph nodes: preferential expression of interleukin-1 beta and interferon-gamma genes. Hum Pathol. 1992 Mar;23(3):317–323. doi: 10.1016/0046-8177(92)90114-i. [DOI] [PubMed] [Google Scholar]
  8. Emilie D., Peuchmaur M., Maillot M. C., Crevon M. C., Brousse N., Delfraissy J. F., Dormont J., Galanaud P. Production of interleukins in human immunodeficiency virus-1-replicating lymph nodes. J Clin Invest. 1990 Jul;86(1):148–159. doi: 10.1172/JCI114678. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Essner R., Rhoades K., McBride W. H., Morton D. L., Economou J. S. IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. J Immunol. 1989 Jun 1;142(11):3857–3861. [PubMed] [Google Scholar]
  10. Haanen J. B., de Waal Malefijt R., Res P. C., Kraakman E. M., Ottenhoff T. H., de Vries R. R., Spits H. Selection of a human T helper type 1-like T cell subset by mycobacteria. J Exp Med. 1991 Sep 1;174(3):583–592. doi: 10.1084/jem.174.3.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heeger P., Wolf G., Meyers C., Sun M. J., O'Farrell S. C., Krensky A. M., Neilson E. G. Isolation and characterization of cDNA from renal tubular epithelium encoding murine Rantes. Kidney Int. 1992 Jan;41(1):220–225. doi: 10.1038/ki.1992.31. [DOI] [PubMed] [Google Scholar]
  12. Howard M., O'Garra A. Biological properties of interleukin 10. Immunol Today. 1992 Jun;13(6):198–200. doi: 10.1016/0167-5699(92)90153-X. [DOI] [PubMed] [Google Scholar]
  13. Issekutz T. B. Dual inhibition of VLA-4 and LFA-1 maximally inhibits cutaneous delayed-type hypersensitivity-induced inflammation. Am J Pathol. 1993 Nov;143(5):1286–1293. [PMC free article] [PubMed] [Google Scholar]
  14. Issekutz T. B. Effects of six different cytokines on lymphocyte adherence to microvascular endothelium and in vivo lymphocyte migration in the rat. J Immunol. 1990 Mar 15;144(6):2140–2146. [PubMed] [Google Scholar]
  15. Kameyoshi Y., Dörschner A., Mallet A. I., Christophers E., Schröder J. M. Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992 Aug 1;176(2):587–592. doi: 10.1084/jem.176.2.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kaplan G., Luster A. D., Hancock G., Cohn Z. A. The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin. J Exp Med. 1987 Oct 1;166(4):1098–1108. doi: 10.1084/jem.166.4.1098. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Köhler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993 Mar 18;362(6417):245–248. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar]
  18. Mantovani A., Bussolino F., Dejana E. Cytokine regulation of endothelial cell function. FASEB J. 1992 May;6(8):2591–2599. doi: 10.1096/fasebj.6.8.1592209. [DOI] [PubMed] [Google Scholar]
  19. Mantovani A., Dejana E. Cytokines as communication signals between leukocytes and endothelial cells. Immunol Today. 1989 Nov;10(11):370–375. doi: 10.1016/0167-5699(89)90270-3. [DOI] [PubMed] [Google Scholar]
  20. Oppenheim J. J., Zachariae C. O., Mukaida N., Matsushima K. Properties of the novel proinflammatory supergene "intercrine" cytokine family. Annu Rev Immunol. 1991;9:617–648. doi: 10.1146/annurev.iy.09.040191.003153. [DOI] [PubMed] [Google Scholar]
  21. Peuchmaur M., Emilie D., Crevon M. C., Solal-Celigny P., Maillot M. C., Lemaigre G., Galanaud P. IL-2 mRNA expression in Tac-positive malignant lymphomas. Am J Pathol. 1990 Feb;136(2):383–390. [PMC free article] [PubMed] [Google Scholar]
  22. Rathanaswami P., Hachicha M., Sadick M., Schall T. J., McColl S. R. Expression of the cytokine RANTES in human rheumatoid synovial fibroblasts. Differential regulation of RANTES and interleukin-8 genes by inflammatory cytokines. J Biol Chem. 1993 Mar 15;268(8):5834–5839. [PubMed] [Google Scholar]
  23. Rot A., Krieger M., Brunner T., Bischoff S. C., Schall T. J., Dahinden C. A. RANTES and macrophage inflammatory protein 1 alpha induce the migration and activation of normal human eosinophil granulocytes. J Exp Med. 1992 Dec 1;176(6):1489–1495. doi: 10.1084/jem.176.6.1489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schall T. J., Bacon K., Toy K. J., Goeddel D. V. Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature. 1990 Oct 18;347(6294):669–671. doi: 10.1038/347669a0. [DOI] [PubMed] [Google Scholar]
  25. Schall T. J. Biology of the RANTES/SIS cytokine family. Cytokine. 1991 May;3(3):165–183. doi: 10.1016/1043-4666(91)90013-4. [DOI] [PubMed] [Google Scholar]
  26. Schall T. J., Jongstra J., Dyer B. J., Jorgensen J., Clayberger C., Davis M. M., Krensky A. M. A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988 Aug 1;141(3):1018–1025. [PubMed] [Google Scholar]
  27. Schall T. J., O'Hehir R. E., Goeddel D. V., Lamb J. R. Uncoupling of cytokine mRNA expression and protein secretion during the induction phase of T cell anergy. J Immunol. 1992 Jan 15;148(2):381–387. [PubMed] [Google Scholar]
  28. Taub D. D., Lloyd A. R., Conlon K., Wang J. M., Ortaldo J. R., Harada A., Matsushima K., Kelvin D. J., Oppenheim J. J. Recombinant human interferon-inducible protein 10 is a chemoattractant for human monocytes and T lymphocytes and promotes T cell adhesion to endothelial cells. J Exp Med. 1993 Jun 1;177(6):1809–1814. doi: 10.1084/jem.177.6.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thomas P. D., Hunninghake G. W. Current concepts of the pathogenesis of sarcoidosis. Am Rev Respir Dis. 1987 Mar;135(3):747–760. doi: 10.1164/arrd.1987.135.3.747. [DOI] [PubMed] [Google Scholar]
  30. Tsicopoulos A., Hamid Q., Varney V., Ying S., Moqbel R., Durham S. R., Kay A. B. Preferential messenger RNA expression of Th1-type cells (IFN-gamma+, IL-2+) in classical delayed-type (tuberculin) hypersensitivity reactions in human skin. J Immunol. 1992 Apr 1;148(7):2058–2061. [PubMed] [Google Scholar]
  31. Williams G. T., Williams W. J. Granulomatous inflammation--a review. J Clin Pathol. 1983 Jul;36(7):723–733. doi: 10.1136/jcp.36.7.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yamamura M., Uyemura K., Deans R. J., Weinberg K., Rea T. H., Bloom B. R., Modlin R. L. Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science. 1991 Oct 11;254(5029):277–279. doi: 10.1126/science.254.5029.277. [DOI] [PubMed] [Google Scholar]
  33. Yamamura M., Wang X. H., Ohmen J. D., Uyemura K., Rea T. H., Bloom B. R., Modlin R. L. Cytokine patterns of immunologically mediated tissue damage. J Immunol. 1992 Aug 15;149(4):1470–1475. [PubMed] [Google Scholar]
  34. te Velde A. A., Huijbens R. J., Heije K., de Vries J. E., Figdor C. G. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood. 1990 Oct 1;76(7):1392–1397. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES