CNS Transplants and the Host Immune Response: The Blood-Brain Barrier and Immunological Privilege within the Mammalian Brain

  • Richard D. Broadwell
  • Belinda J. Baker
  • William F. Hickey


Survival of fetal mammalian brain tissue or of cell suspensions grafted into the adult mammalian brain is dependent upon the graft developing a vascular network supplied with host blood and failure of the host immune system to reject the graft as foreign tissue. The mammalian CNS has long been suspected to be a site of “immunological privilege” where constituents of the peripheral immune system do not venture. This suspected privilege is attributed to the absence of easily identifiable antigen presenting cells (e.g., cells expressing MHC class II antigen constitutively), the absence of lymphatic drainage, and the presence of the blood-brain barrier (for reviews see Head and Billingham, 1985; Widner and Brundin, 1988; Sloan et al., 1991).


Major Histocompatibility Complex Major Histocompatibility Complex Class Perivascular Cell Pial Surface Major Histocompatibility Complex Antigen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baker, B.J., and Broadwell, R.D., 1993, Balls and brains: I. Immunological privilege for CNS grafts, Soc. Neurosci. Abstr. 19:1740.Google Scholar
  2. Bergman, H., Nagy, J.I., and Granholm, A-C., 1995, Intracranial transplantation and survival of tuberomammillary histaminergic neurons, Neurosci. 64:61.CrossRefGoogle Scholar
  3. Broadwell, R.D., Baker, B.J., Ebert, P.S., and Hickey, W.F., 1994, Allografts of CNS tissue possess a blood-brain barrier: III. Neuropathological, methodological, and immunological considerations, Micros. Res. and Tech. 27:471.CrossRefGoogle Scholar
  4. Broadwell, R.D., and Banks, W.A, 1993, A cell biological perspective for the transcytosis of peptides and proteins through the mammalian blood-brain fluid barriers, in: “The Blood-Brain Barrier Molecular and Cellular Biology,” W.M. Pardridge, ed., Raven Press, New York.Google Scholar
  5. Broadwell, R.D., Charlton, H.M., Balin, B.J., and Salcman, M., 1987, Angioarchitecture of the CNS, pituitary gland, and intracerebral grafts revealed with peroxidase cytochemistry, J. Comp. Neurol. 260:47.PubMedCrossRefGoogle Scholar
  6. Broadwell, R.D., Charlton, H.M., Ebert, P.S., Hickey, W.F., Shirazi, Y., Villegas, J., and Wolf, A.L., 1991, Allografts of CNS tissue possess a blood-brain barrier: II. Angiogenesis in solid tissue and cell suspension grafts, Exp. Neurol. 112:1.PubMedCrossRefGoogle Scholar
  7. Broadwell, R.D., Charlton, H.M., Ganong, W.F., Salcman, M., and Sofroniew, M.V., 1989, Allografts of CNS tissue possess a blood-brain barrier: I. Grafts of medial preoptic area in hypogonadal mice, Exp. Neurol. 105:135.PubMedCrossRefGoogle Scholar
  8. Broadwell, R.D., and Sofroniew, M.V., 1993, Serum proteins by-pass the blood-brain barrier for extracellular entry to the central nervous system, Exp. Neurol. 120:245.PubMedCrossRefGoogle Scholar
  9. Cserr, H.F., and Knopf, P.M., 1992, Cervical lymphatics, the blood-brain barrier and the immunoreactivity of the brain: A new review, Immunol. Today 13:507.PubMedCrossRefGoogle Scholar
  10. Fontana, A., Fierz, W., and Wekerle, H., 1984, Astrocytes present myelin basic protein to encephalitogenic T-cell lines, Nature 307:273.PubMedCrossRefGoogle Scholar
  11. Head, J.R., and Billingham, R.E., 1985, Immunologically privileged sites in transplantation immunology and oncology, Perspect. Biol. Med. 29:115.PubMedGoogle Scholar
  12. Hickey, W.F., and Kimura, H., 1988, Perivascular microglial cells of the CNS are bone marrow derived and present antigen in vivo, Science 239:290.PubMedCrossRefGoogle Scholar
  13. Hickey, W.F., Vass, K., and Lassmann, H., 1992, Bone marrow-derived elements in the central nervous system: An immunohistochemical and ultrastructural survey of rat chimeras, J. Neuropath. Exp. Neurol. 51:246.PubMedCrossRefGoogle Scholar
  14. Maddocks, S., and Setchell, B.P., 1990, Recent evidence for immune privilege in the testis, J. Reprod. Immunol. 18:9.PubMedCrossRefGoogle Scholar
  15. Male, D.K., Pryce, G., and Hughes, C.C.W., 1987, Antigen presentation in brain: MHC induction on brain endothelium and astrocytes compared, Immunol. 60:453.Google Scholar
  16. Mason, D.W., Charlton, H.M., Jones, A.J., Lavy, C.B.D., Puklavec, M., and Simmonds, S.J., 1986, The fate of allogeneic and xenogeneic tissue transplanted into the third ventricle of rodents, Neurosci. 19:685.CrossRefGoogle Scholar
  17. Medawar, P.B., 1948, Immunity to homologous grafted skin. III. The fate of skin homografts transplanted to the brain, to subcutaneous tissue and to the anterior chamber of the eye, Brit. J. Exp. Path. 29:58.PubMedGoogle Scholar
  18. Risau, W., Engelhardt, B., and Wekerle, H, 1990, Immune function of the blood-brain barrier: Incomplete presentation of protein (auto-)antigens by rat brain microvascular endothelium in vitro, J. Cell Biol. 110:1757.PubMedCrossRefGoogle Scholar
  19. Sloan, DJ., Baker, B.J., Puklavec, M., and Charlton, H.M., 1990, The effect of site of transplantation and histocompatibility differences on the survival of neural tissue transplanted to the CNS of inbred rat strains, Prog. Brain Res. 82:141.PubMedCrossRefGoogle Scholar
  20. Sloan, D.J., Wood, M.J., and Charlton, H.M., 1991, The immune response to intracerebral neural grafts, Trends Neurosci. 14:341.PubMedCrossRefGoogle Scholar
  21. Widner, H., and Brundin, P., 1988, Immunological aspects of grafting in the mammalian central nervous system. A review and speculative synthesis. Brain Res. Rev. 13:287.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Richard D. Broadwell
    • 1
  • Belinda J. Baker
    • 2
  • William F. Hickey
    • 3
  1. 1.Office of Research IntegrityUnited States Public Health ServiceRockvilleUSA
  2. 2.Laboratory of Molecular Medicine and NeuroscienceNational Institutes of HealthBethesdaUSA
  3. 3.Department of PathologyDartmouth School of MedicineLebanonUSA

Personalised recommendations