Skip to main content
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2002 Dec 10;46(1):25–31. doi: 10.1016/0165-5728(93)90230-V

Trafficking of activated cytotoxic T lymphocytes into the central nervous system: Use of a transgenic model

Michael BA Oldstone a,, Peter J Southern b
PMCID: PMC7119476  PMID: 8360331

Abstract

We have used cell or tissue-specific promoters to express lymphocytic choriomeningitis virus (LCMV) proteins in selected cells in independent lines of transgenic mice. Upon adoptive transfers into these mice, MHC-restricted LCMV-specific cytotoxic T lymphocytes homed specifically to either the choroid plexus (SV40 promoter) or β cells of the islets of Langerhans (rat insulin promoter). The availability of promoters specific for neurons, oligodendrocytes and astrocytes makes this approach compelling for evaluating T cell trafficking into the CNS and for analyzing antigen presentation in vivo in the CNS.

Keywords: Trafficking, Central nervous system, Cytotoxic T lymphocytes

References

  1. Campbell I.L., Oldstone M.B.A., Mucke L. Society for Neuroscience; Anaheim, CA: 1992. Neurologic disease induced in transgenic mice by the astrocyte-specific expression of interleukin-6. October 25–30. [Google Scholar]
  2. Chan W., Javanovic T., Lukie M. Infiltration of immune T cells in the brain of mice with herpes simplex virus-induced encephalitis. J. Neuroimmunol. 1989;23:195. doi: 10.1016/0165-5728(89)90051-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. De la Torre J.C., Oldstone M.B.A. Vol. 89. 1992. Selective disruption of growth hormone transcription machinery by viral infection; pp. 9939–9943. (Proc. Natl. Acad. Sci. USA). [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dutko F.J., Oldstone M.B.A. Genomic and biological variation among commonly used lymphocytic choriomeningitis virus strains. J. Gen. Virol. 1983;64:1689–1689. doi: 10.1099/0022-1317-64-8-1689. [DOI] [PubMed] [Google Scholar]
  5. Falk K., Rotzscke O., Stevanovie S. Allele-specific motifs rrevealed by sequncing of self-peptides eluted from MHC molecules. Nature. 1991;351:290–296. doi: 10.1038/351290a0. [DOI] [PubMed] [Google Scholar]
  6. Feigenbaum L., Hinrichs S.H., Jay G. JC virus and simian virus 40 enhancers and transforming proteins: Role in determining tissue specificity and pathogenicity in transgenic mice. J. Virol. 1992;66:1176–1182. doi: 10.1128/jvi.66.2.1176-1182.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gairin J.E., Oldstone M.B.A. Design of high-affinity major histocompatibility complex-specific antagonist peptides that inhibit cytotoxic T lymphocyte activity: Implications for control of viral disease. J. Virol. 1992;66:6755–6762. doi: 10.1128/jvi.66.11.6755-6762.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hickey W.F., Hsu B.L., Kimura H. T-lymphocyte entry into the central nervous system. J. Neurosci. Res. 1991;28:254–260. doi: 10.1002/jnr.490280213. [DOI] [PubMed] [Google Scholar]
  9. Joly E., Mucke L., Oldstone M.B.A. Viral persistence in neurons explained by lack of major histocompatibility complex class I expression. Science. 1991;253:1283–1285. doi: 10.1126/science.1891717. [DOI] [PubMed] [Google Scholar]
  10. Klavinskis L.S., Whitton J.L., Oldstone M.B.A. Efficiency and effectiveness of cloned virus specific cytotoxic T lymphocytes in vivo. J. Immunol. 1989;143:2013–2016. [PubMed] [Google Scholar]
  11. Klavinskis L.S., Whitton J.L., Joly E., Oldstone M.B.A. Vaccination and protection from a lethal viral infection: Identification, incorporation and use of a cytotoxic T lymphocyte glycoprotein epitope. Virology. 1990;178:393–400. doi: 10.1016/0042-6822(90)90336-p. [DOI] [PubMed] [Google Scholar]
  12. Marks J., Lin J., Miller D., Lozano G., Herbert J., Levine A.J. The expression of viral aellular genes in papillomas of the choroid plexus induced in transgenic mice. Prog. Clin. Biol. Res.Prog. Clin. Biol. Res. 1988;284:1630186. [PubMed] [Google Scholar]
  13. Messing A., Pinkert C.A., Palmiter R.D., Brinster R.L. Developmental study of SV40 large T antigen expression in transgenic mice. Oncogene Res. 1988;3:87–97. [PubMed] [Google Scholar]
  14. Mucke L., Oldstone M.B.A., Morris J.C., Nerenberg M.I. Rapid activation of astrocyte-specific expression of GFAP-lacZ transgene by focal injury. New Biologist. 1991;3:465–474. [PubMed] [Google Scholar]
  15. Mucke L., Forss-Petter S., Goldgaber D., Johnson W., Picard E., Rockenstein E., Abraham C. Transgenic models to study the pathogenic role of mutated and non-mutated forms of human amyloid proteins in the development of Alzheimer's disease (AD). Third International Conference on Alzheimer's Disease and Related Disorders; Abano Terme (Padova), Italy, July 12–17; 1992. [Google Scholar]
  16. Mucke L. Transgenic models to study diseases of the nervous system: An in vivo approach to dissect complex pathogenetic networks. Proc. Symp. Immunology II; Freiburg, Germany; 1993. in press. [Google Scholar]
  17. Mucke L., Rockenstein E.M. Prolonged delivery of transgene products to specific brain regions by migratory astrocyte grafts. Transgene. 1993 in press. [Google Scholar]
  18. Ohashi P.S., Oehen S., Buerki K., Ohashi C.T., Odermatt B., Malissen B., Zinkernagel R.M., Hengartner H. Ablation of “tolerance” and induction of diabetes by virus infection in viral antigen transgenic mice. Cell. 1991;65:305–317. doi: 10.1016/0092-8674(91)90164-t. [DOI] [PubMed] [Google Scholar]
  19. Oldstone M.B.A., Blount P., Southern P.J., Lampert P.W. Cytoimmunotherapy for persistent virus infection: Unique clearance pattern from the central nervous system. Nature. 1986;321:239–243. doi: 10.1038/321239a0. [DOI] [PubMed] [Google Scholar]
  20. Oldstone M.B.A. Springer-Verlag; Berlin: 1987. Arenaviruses: Biology and Immunotherapy, Current Topics in Microbiology and Immunology. [PubMed] [Google Scholar]
  21. Oldstone M.B.A., Whitton J.L., Lewicki H., Tishon A. Fine dissection of a nine amino acid glycoprotein epitope, a major determinant recognized by lymphocytic choriomeningitis virus specific class I restricted H-2Db cytotoxic T lymphocytes. J. Exp. Med. 1988;168:559–570. doi: 10.1084/jem.168.2.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Oldstone M.B.A. Molecular anatomy of viral persistence. J. Virol. 1991;65:6381–6386. doi: 10.1128/jvi.65.12.6381-6386.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Oldstone M.B.A., Nerenberg M., Southern P., Price J., Lewicki H. Virus infection triggers insulin dependent diabetes mellitus in a transgenic model: Role of anti-self (virus) immune response. Cell. 1991;65:319–331. doi: 10.1016/0092-8674(91)90165-u. [DOI] [PubMed] [Google Scholar]
  24. Rall G.F., Mucke L., Oldstone M.B.A. American Society for Virology, Cornell University; Ithaca, New York: 1992. Transgenic mice which express histocompatibility molecules targeted to unique cells of the central nervous system. July 11–15. [Google Scholar]
  25. Rall G.F., Mucke L., Oldstone M.B.A. Targeting specific host and viral genes to cells of the central nervous system: Transgenic studies. NIH AIDS Postdoctoral Fellows Meeting; Albuquerque, NM. March 29–April 4; 1993. [Google Scholar]
  26. Sinha A.A., Lopez M.T., McDevitt H.O. Autoimmune diseases: The failure of self tolerance. Science. 1990;248:1380–1387. doi: 10.1126/science.1972595. [DOI] [PubMed] [Google Scholar]
  27. Southern P.J., Singh M.K., Riviere Y., Jacoby D.R., Buchmeier M.J., Oldstone M.B.A. Molecular characterization of the genome S RNA segment from lymphocytic choriomeningitis virus. Virology. 1987;157:145–155. doi: 10.1016/0042-6822(87)90323-0. [DOI] [PubMed] [Google Scholar]
  28. Toggas S.M., Rockenstein E., Mucke L. The effects of cerebral HIV-1 gp120 expression in transgenic mice. NIH AIDS Postdoctoral Fellows Meeting; Albuquerque, NM. March 29–April 4; 1993. [Google Scholar]
  29. Townsend A.R.M., Rothbard J., Gotch F.M., Bahadur G., Wraith D., McMichael A.J. The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell. 1986;44:959–968. doi: 10.1016/0092-8674(86)90019-x. [DOI] [PubMed] [Google Scholar]
  30. Van Bleek G.M., Nathenson S.G. Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule. Nature. 1990;348:213–216. doi: 10.1038/348213a0. [DOI] [PubMed] [Google Scholar]
  31. Vanderbark A., Offner H., Reshef T., Fritz R., Chou C., Cohen I. Specificity of T lymphocyte lines for peptides of myelin basic protein. J. Immunol. 1985;135:229–233. [PubMed] [Google Scholar]
  32. Von Herrath M., Paulk J., Lewicki H., Tishon T., Oldstone M.B.A. American Society for Virology, Cornell University; Ithaca, NY: 1992. Virus induced autoimmunity: Ability of various LCMV strains to cause insulin dependent diabetes mellitus in a RIP-LCMV-ARM transgenic mouse model. July 11–15. [Google Scholar]
  33. Watanabe R., Wege H., ter Meulen V. Adoptive transfer of EAE-like lesions from rats with coronavirus-induced demyelinating encephalomyelitis. Nature. 1983;305:150–153. doi: 10.1038/305150a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wekerte H., Linington C., Meyermann R. Cellular immune reactivity within the CNS. Trends Neurosci. 1986;9:271. [Google Scholar]
  35. Whitton J.L., Gebhard J.R., Lewicki H., Tishon A., Oldstone M.B.A. Molecular definition of a major cytotoxic T lymphocyte epitope in the glycoprotein of lymphocytic choriomeningitis virus. J. Virol. 1988;62:687–695. doi: 10.1128/jvi.62.3.687-695.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Whitton J.L., Southern P.J., Oldstone M.B.A. Analyses of the cytotoxic T lymphocyte responses to glycoprotein and nucleoprotein components of lymphocytic choriomeningitis virus. Virology. 1988;162:321–327. doi: 10.1016/0042-6822(88)90471-0. [DOI] [PubMed] [Google Scholar]
  37. Whitton J.L., Tishon A., Lewicki H., Gebhard J., Cook T., Salvato M., Joly E., Oldstone M.B.A. Molecular analyses of a five amino acid cytotoxic T lymphocyte (CTL) epitope: An immunodominant region which induces nonreciprocal CTL cross-reactivity. J. Virol. 1989;63:4303–4310. doi: 10.1128/jvi.63.10.4303-4310.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yanagi Y., Tishon A., Lewicki H., Cubitt B.A., Oldstone M.B.A. Diversity of T-cell receptors in virus-specific cytotoxic T lymphocytes recognizing three distinct viral epitopes restricted by a single major histocompatibility complex molecule. J. Virol. 1992;66:2527–2531. doi: 10.1128/jvi.66.4.2527-2531.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Zinkernagel R.M., Doherty P.C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974;248:701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Neuroimmunology are provided here courtesy of Elsevier

RESOURCES