Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Jul;149(1):187–194.

In situ analysis of B7-2 costimulatory, major histocompatibility complex class II, and adhesion molecule expression in schistosomal egg granulomas.

A Rathore 1, C Sacristán 1, D E Ricklan 1, P O Flores Villanueva 1, M J Stadecker 1
PMCID: PMC1865239  PMID: 8686742

Abstract

Immunopathological damage in schistosomiasis consist of egg granuloma formation, which is a hypersensitivity reaction mediated by antigen-specific CD4+ T helper (Th) lymphocytes. Th cells are dependent on accessory cell-bound co-stimulatory signals for activation. The B7 molecules provide critical costimulation, as in their absence T cells are rendered unresponsive. We investigated the kinetics of B7-2 molecule expression in schistosomal egg granulomas by immunocytochemical analysis in situ. We also monitored major histocompatibility complex (MHC) class II, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, as well as the presence of macrophages, T cells, and B cells. B7-2 expression was elevated in cells of the large granulomas of the acute (6-1/2 week) infection, and sharply declined thereafter. MHC class II expression was similarly elevated in the acute granulomas, but in contrast to B7-2, remained relatively constant throughout 12 1/2 weeks of infection. Moreover, ICAM-1 and VCAM-1 were expressed in acute and chronic granulomas. However, whereas ICAM-1 was constitutively expressed in normal liver, VCAM-1 was dramatically induced in the livers upon onset of disease. The findings suggest that the acute granulomas are rich in accessory cells with overall phenotypic configurations that support Th-cell activation, although at subsequent times, granulomas contain increasing numbers of B7-poor accessory cells capable of inducing Th-cell unresponsiveness. Thus, cellular interactions in early granulomas may be able to amplify egg-induced immunopathology, whereas interactions taking place in succeeding granulomas appear to precipitate its down-regulation.

Full text

PDF
187

Images in this article

190Figure 1
on p.190

Selected References

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

  1. ANDRADE Z. A. WARREN KS: MILD PROLONGED SCHISTOSOMIASIS IN MICE: ALTERATIONS IN HOST RESPONSE WITH TIME AND THE DEVELOPMENT OF PORTAL FIBROSIS. Trans R Soc Trop Med Hyg. 1964 Jan;58:53–57. doi: 10.1016/0035-9203(64)90068-9. [DOI] [PubMed] [Google Scholar]
  2. Adams D. H., Hubscher S. G., Shaw J., Rothlein R., Neuberger J. M. Intercellular adhesion molecule 1 on liver allografts during rejection. Lancet. 1989 Nov 11;2(8672):1122–1125. doi: 10.1016/s0140-6736(89)91489-x. [DOI] [PubMed] [Google Scholar]
  3. Bacchi C. E., Marsh C. L., Perkins J. D., Carithers R. L., Jr, McVicar J. P., Hudkins K. L., Benjamin C. D., Harlan J. M., Lobb R., Alpers C. E. Expression of vascular cell adhesion molecule (VCAM-1) in liver and pancreas allograft rejection. Am J Pathol. 1993 Feb;142(2):579–591. [PMC free article] [PubMed] [Google Scholar]
  4. Bevilacqua M. P. Endothelial-leukocyte adhesion molecules. Annu Rev Immunol. 1993;11:767–804. doi: 10.1146/annurev.iy.11.040193.004003. [DOI] [PubMed] [Google Scholar]
  5. Bogen S. A., Flores Villanueva P. O., McCusker M. E., Fogelman I., Garifallou M., el-Attar E. S., Kwan P., Stadecker M. J. In situ analysis of cytokine responses in experimental murine schistosomiasis. Lab Invest. 1995 Aug;73(2):252–258. [PubMed] [Google Scholar]
  6. Boros D. L. Immunopathology of Schistosoma mansoni infection. Clin Microbiol Rev. 1989 Jul;2(3):250–269. doi: 10.1128/cmr.2.3.250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen C., Nabavi N. In vitro induction of T cell anergy by blocking B7 and early T cell costimulatory molecule ETC-1/B7-2. Immunity. 1994 May;1(2):147–154. doi: 10.1016/1074-7613(94)90108-2. [DOI] [PubMed] [Google Scholar]
  8. Chensue S. W., Boros D. L. Population dynamics of T and B lymphocytes in the lymphoid organs, circulation, and granulomas of mice infected with Schistosoma mansoni. Am J Trop Med Hyg. 1979 Mar;28(2):291–299. doi: 10.4269/ajtmh.1979.28.291. [DOI] [PubMed] [Google Scholar]
  9. Chensue S. W., Warmington K. S., Hershey S. D., Terebuh P. D., Othman M., Kunkel S. L. Evolving T cell responses in murine schistosomiasis. Th2 cells mediate secondary granulomatous hypersensitivity and are regulated by CD8+ T cells in vivo. J Immunol. 1993 Aug 1;151(3):1391–1400. [PubMed] [Google Scholar]
  10. Dustin M. L., Rothlein R., Bhan A. K., Dinarello C. A., Springer T. A. Induction by IL 1 and interferon-gamma: tissue distribution, biochemistry, and function of a natural adherence molecule (ICAM-1). J Immunol. 1986 Jul 1;137(1):245–254. [PubMed] [Google Scholar]
  11. Elices M. J., Osborn L., Takada Y., Crouse C., Luhowskyj S., Hemler M. E., Lobb R. R. VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site. Cell. 1990 Feb 23;60(4):577–584. doi: 10.1016/0092-8674(90)90661-w. [DOI] [PubMed] [Google Scholar]
  12. Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fiorentino D. F., Zlotnik A., Vieira P., Mosmann T. R., Howard M., Moore K. W., O'Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991 May 15;146(10):3444–3451. [PubMed] [Google Scholar]
  14. Flores Villanueva P. O., Chikunguwo S. M., Harris T. S., Stadecker M. J. Role of IL-10 on antigen-presenting cell function for schistosomal egg-specific monoclonal T helper cell responses in vitro and in vivo. J Immunol. 1993 Sep 15;151(6):3192–3198. [PubMed] [Google Scholar]
  15. Flores Villanueva P. O., Harris T. S., Ricklan D. E., Stadecker M. J. Macrophages from schistosomal egg granulomas induce unresponsiveness in specific cloned Th-1 lymphocytes in vitro and down-regulate schistosomal granulomatous disease in vivo. J Immunol. 1994 Feb 15;152(4):1847–1855. [PubMed] [Google Scholar]
  16. Flores Villanueva P. O., Reiser H., Stadecker M. J. Regulation of T helper cell responses in experimental murine schistosomiasis by IL-10. Effect on expression of B7 and B7-2 costimulatory molecules by macrophages. J Immunol. 1994 Dec 1;153(11):5190–5199. [PubMed] [Google Scholar]
  17. Freeman G. J., Borriello F., Hodes R. J., Reiser H., Gribben J. G., Ng J. W., Kim J., Goldberg J. M., Hathcock K., Laszlo G. Murine B7-2, an alternative CTLA4 counter-receptor that costimulates T cell proliferation and interleukin 2 production. J Exp Med. 1993 Dec 1;178(6):2185–2192. doi: 10.1084/jem.178.6.2185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gimmi C. D., Freeman G. J., Gribben J. G., Gray G., Nadler L. M. Human T-cell clonal anergy is induced by antigen presentation in the absence of B7 costimulation. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6586–6590. doi: 10.1073/pnas.90.14.6586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Iacomini J., Ricklan D. E., Stadecker M. J. T cells expressing the gamma delta T cell receptor are not required for egg granuloma formation in schistosomiasis. Eur J Immunol. 1995 Apr;25(4):884–888. doi: 10.1002/eji.1830250404. [DOI] [PubMed] [Google Scholar]
  20. Inaba K., Witmer-Pack M., Inaba M., Hathcock K. S., Sakuta H., Azuma M., Yagita H., Okumura K., Linsley P. S., Ikehara S. The tissue distribution of the B7-2 costimulator in mice: abundant expression on dendritic cells in situ and during maturation in vitro. J Exp Med. 1994 Nov 1;180(5):1849–1860. doi: 10.1084/jem.180.5.1849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Langley J. G., Boros D. L. T-lymphocyte responsiveness in murine schistosomiasis mansoni is dependent upon the adhesion molecules intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, and very late antigen-4. Infect Immun. 1995 Oct;63(10):3980–3986. doi: 10.1128/iai.63.10.3980-3986.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Linsley P. S., Brady W., Urnes M., Grosmaire L. S., Damle N. K., Ledbetter J. A. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991 Sep 1;174(3):561–569. doi: 10.1084/jem.174.3.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Linsley P. S., Clark E. A., Ledbetter J. A. T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5031–5035. doi: 10.1073/pnas.87.13.5031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Lukacs N. W., Chensue S. W., Strieter R. M., Warmington K., Kunkel S. L. Inflammatory granuloma formation is mediated by TNF-alpha-inducible intercellular adhesion molecule-1. J Immunol. 1994 Jun 15;152(12):5883–5889. [PubMed] [Google Scholar]
  25. Lukacs N. W., Kunkel S. L., Strieter R. M., Warmington K., Chensue S. W. The role of macrophage inflammatory protein 1 alpha in Schistosoma mansoni egg-induced granulomatous inflammation. J Exp Med. 1993 Jun 1;177(6):1551–1559. doi: 10.1084/jem.177.6.1551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mathew R. C., Boros D. L. Anti-L3T4 antibody treatment suppresses hepatic granuloma formation and abrogates antigen-induced interleukin-2 production in Schistosoma mansoni infection. Infect Immun. 1986 Dec;54(3):820–826. doi: 10.1128/iai.54.3.820-826.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. O'Garra A., Chang R., Go N., Hastings R., Haughton G., Howard M. Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10. Eur J Immunol. 1992 Mar;22(3):711–717. doi: 10.1002/eji.1830220314. [DOI] [PubMed] [Google Scholar]
  28. O'Garra A., Stapleton G., Dhar V., Pearce M., Schumacher J., Rugo H., Barbis D., Stall A., Cupp J., Moore K. Production of cytokines by mouse B cells: B lymphomas and normal B cells produce interleukin 10. Int Immunol. 1990;2(9):821–832. doi: 10.1093/intimm/2.9.821. [DOI] [PubMed] [Google Scholar]
  29. Secor W. E., dos Reis M. G., Ramos E. A., Matos E. P., Reis E. A., do Carmo T. M., Harn D. A., Jr Soluble intercellular adhesion molecules in human schistosomiasis: correlations with disease severity and decreased responsiveness to egg antigens. Infect Immun. 1994 Jul;62(7):2695–2701. doi: 10.1128/iai.62.7.2695-2701.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sher A., Fiorentino D., Caspar P., Pearce E., Mosmann T. Production of IL-10 by CD4+ T lymphocytes correlates with down-regulation of Th1 cytokine synthesis in helminth infection. J Immunol. 1991 Oct 15;147(8):2713–2716. [PubMed] [Google Scholar]
  31. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  32. Stadecker M. J., Flores Villanueva P. O. Accessory cell signals regulate Th-cell responses: from basic immunology to a model of helminthic disease. Immunol Today. 1994 Dec;15(12):571–574. doi: 10.1016/0167-5699(94)90219-4. [DOI] [PubMed] [Google Scholar]
  33. Stadecker M. J. The role of T-cell anergy in the immunomodulation of schistosomiasis. Parasitol Today. 1992 Jun;8(6):199–204. doi: 10.1016/0169-4758(92)90264-3. [DOI] [PubMed] [Google Scholar]
  34. Stadecker M. J., Wright J. A. Distribution and kinetics of mononuclear phagocytes in granulomas elicited by eggs of Schistosoma mansoni. Am J Pathol. 1984 Aug;116(2):245–252. [PMC free article] [PubMed] [Google Scholar]
  35. Steinhoff G., Behrend M., Pichlmayr R. Induction of ICAM-1 on hepatocyte membranes during liver allograft rejection and infection. Transplant Proc. 1990 Oct;22(5):2308–2309. [PubMed] [Google Scholar]
  36. Wynn T. A., Eltoum I., Cheever A. W., Lewis F. A., Gause W. C., Sher A. Analysis of cytokine mRNA expression during primary granuloma formation induced by eggs of Schistosoma mansoni. J Immunol. 1993 Aug 1;151(3):1430–1440. [PubMed] [Google Scholar]
  37. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES