Skip to main content
Immunology logoLink to Immunology
. 1989 Feb;66(2):207–212.

Antigen presentation in brain: brain endothelial cells are poor stimulators of T-cell proliferation.

G Pryce 1, D Male 1, J Sedgwick 1
PMCID: PMC1385088  PMID: 2784409

Abstract

The capacity of rat brain capillary endothelium to present antigen to primed peripheral lymph node cells or to ovalbumin-specific T-cell lines was examined in vitro. Brain endothelium can present antigen, but it is generally ineffective at stimulating T-cell division. Division is only seen when indomethacin is included in the cultures to suppress eicosanoid production. Even under these conditions an endothelial monolayer is only 1/40 as effective as a thymocyte monolayer in stimulating division. The failure to act as an effective antigen presenting tissue is not due to lack of IL-1 production, nor is it related to the extended time required to induce MHC class II molecules on these cells. In the presence of high levels of antigen-specific T cells, the endothelium appears to be subject to cytotoxic damage, so that T-cell stimulation is lowest with higher numbers of T cells--the opposite of that seen with conventional antigen-presenting cells. These findings support the view that brain endothelial cells are not important in stimulating T-cell division during the development of immune reactions in brain, although these cells may be recognizable by class II-restricted cytotoxic cells.

Full text

PDF
211

Selected References

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

  1. Damle N. K., Doyle L. V., Bender J. R., Bradley E. C. Interleukin 2-activated human lymphocytes exhibit enhanced adhesion to normal vascular endothelial cells and cause their lysis. J Immunol. 1987 Mar 15;138(6):1779–1785. [PubMed] [Google Scholar]
  2. Fierz W., Endler B., Reske K., Wekerle H., Fontana A. Astrocytes as antigen-presenting cells. I. Induction of Ia antigen expression on astrocytes by T cells via immune interferon and its effect on antigen presentation. J Immunol. 1985 Jun;134(6):3785–3793. [PubMed] [Google Scholar]
  3. Fontana A., Fierz W. The endothelium--astrocyte immune control system of the brain. Springer Semin Immunopathol. 1985;8(1-2):57–70. doi: 10.1007/BF00197247. [DOI] [PubMed] [Google Scholar]
  4. Fontana A., Kristensen F., Dubs R., Gemsa D., Weber E. Production of prostaglandin E and an interleukin-1 like factor by cultured astrocytes and C6 glioma cells. J Immunol. 1982 Dec;129(6):2413–2419. [PubMed] [Google Scholar]
  5. Giulian D., Baker T. J., Shih L. C., Lachman L. B. Interleukin 1 of the central nervous system is produced by ameboid microglia. J Exp Med. 1986 Aug 1;164(2):594–604. doi: 10.1084/jem.164.2.594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goldstein G. W., Betz A. L., Bowman P. D. Use of isolated brain capillaries and cultured endothelial cells to study the blood-brain barrier. Fed Proc. 1984 Feb;43(2):191–195. [PubMed] [Google Scholar]
  7. Hart D. N., Fabre J. W. Demonstration and characterization of Ia-positive dendritic cells in the interstitial connective tissues of rat heart and other tissues, but not brain. J Exp Med. 1981 Aug 1;154(2):347–361. doi: 10.1084/jem.154.2.347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hughes C. C., Lantos P. L. Brain capillary endothelial cells in vitro lack surface IgG Fc receptors. Neurosci Lett. 1986 Jul 11;68(1):100–106. doi: 10.1016/0304-3940(86)90237-5. [DOI] [PubMed] [Google Scholar]
  9. Hughes C. C., Male D. K., Lantos P. L. Adhesion of lymphocytes to cerebral microvascular cells: effects of interferon-gamma, tumour necrosis factor and interleukin-1. Immunology. 1988 Aug;64(4):677–681. [PMC free article] [PubMed] [Google Scholar]
  10. Male D. K., Pryce G., Hughes C. C. Antigen presentation in brain: MHC induction on brain endothelium and astrocytes compared. Immunology. 1987 Mar;60(3):453–459. [PMC free article] [PubMed] [Google Scholar]
  11. Male D., Pryce G. Synergy between interferons and monokines in MHC induction on brain endothelium. Immunol Lett. 1988 Mar;17(3):267–271. doi: 10.1016/0165-2478(88)90040-5. [DOI] [PubMed] [Google Scholar]
  12. Massa P. T., ter Meulen V., Fontana A. Hyperinducibility of Ia antigen on astrocytes correlates with strain-specific susceptibility to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4219–4223. doi: 10.1073/pnas.84.12.4219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Matsumoto Y., Hara N., Tanaka R., Fujiwara M. Immunohistochemical analysis of the rat central nervous system during experimental allergic encephalomyelitis, with special reference to Ia-positive cells with dendritic morphology. J Immunol. 1986 May 15;136(10):3668–3676. [PubMed] [Google Scholar]
  14. McCarron R. M., Kempski O., Spatz M., McFarlin D. E. Presentation of myelin basic protein by murine cerebral vascular endothelial cells. J Immunol. 1985 May;134(5):3100–3103. [PubMed] [Google Scholar]
  15. Nakamura M., Ross D. T., Briner T. J., Gefter M. L. Cytolytic activity of antigen-specific T cells with helper phenotype. J Immunol. 1986 Jan;136(1):44–47. [PubMed] [Google Scholar]
  16. Perry V. H., Gordon S. Macrophages and microglia in the nervous system. Trends Neurosci. 1988 Jun;11(6):273–277. doi: 10.1016/0166-2236(88)90110-5. [DOI] [PubMed] [Google Scholar]
  17. Pober J. S., Gimbrone M. A., Jr, Collins T., Cotran R. S., Ault K. A., Fiers W., Krensky A. M., Clayberger C., Reiss C. S., Burakoff S. J. Interactions of T lymphocytes with human vascular endothelial cells: role of endothelial cells surface antigens. Immunobiology. 1984 Dec;168(3-5):483–494. doi: 10.1016/s0171-2985(84)80132-1. [DOI] [PubMed] [Google Scholar]
  18. Sedgwick J., Brostoff S., Mason D. Experimental allergic encephalomyelitis in the absence of a classical delayed-type hypersensitivity reaction. Severe paralytic disease correlates with the presence of interleukin 2 receptor-positive cells infiltrating the central nervous system. J Exp Med. 1987 Apr 1;165(4):1058–1075. doi: 10.1084/jem.165.4.1058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Smith J. W., Steiner A. L., Parker C. W. Human lymphocytic metabolism. Effects of cyclic and noncyclic nucleotides on stimulation by phytohemagglutinin. J Clin Invest. 1971 Feb;50(2):442–448. doi: 10.1172/JCI106511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Suzumura A., Mezitis S. G., Gonatas N. K., Silberberg D. H. MHC antigen expression on bulk isolated macrophage-microglia from newborn mouse brain: induction of Ia antigen expression by gamma-interferon. J Neuroimmunol. 1987 Jul-Aug;15(3):263–278. doi: 10.1016/0165-5728(87)90121-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Traugott U., Raine C. S. Multiple sclerosis. Evidence for antigen presentation in situ by endothelial cells and astrocytes. J Neurol Sci. 1985 Jul;69(3):365–370. doi: 10.1016/0022-510x(85)90147-9. [DOI] [PubMed] [Google Scholar]
  22. Vass K., Lassmann H., Wisniewski H. M., Iqbal K. Ultracytochemical distribution of myelin basic protein after injection into the cerebrospinal fluid. Evidence for transport through the blood-brain barrier and binding to the luminal surface of cerebral veins. J Neurol Sci. 1984 Mar;63(3):423–433. doi: 10.1016/0022-510x(84)90165-5. [DOI] [PubMed] [Google Scholar]
  23. Wagner C. R., Vetto R. M., Burger D. R. Expression of I-region-associated antigen (Ia) and interleukin 1 by subcultured human endothelial cells. Cell Immunol. 1985 Jun;93(1):91–104. doi: 10.1016/0008-8749(85)90391-0. [DOI] [PubMed] [Google Scholar]
  24. Wong G. H., Bartlett P. F., Clark-Lewis I., Battye F., Schrader J. W. Inducible expression of H-2 and Ia antigens on brain cells. Nature. 1984 Aug 23;310(5979):688–691. doi: 10.1038/310688a0. [DOI] [PubMed] [Google Scholar]
  25. van der Meide P. H., Dubbeld M., Vijverberg K., Kos T., Schellekens H. The purification and characterization of rat gamma interferon by use of two monoclonal antibodies. J Gen Virol. 1986 Jun;67(Pt 6):1059–1071. doi: 10.1099/0022-1317-67-6-1059. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES