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Department of Neurology

Houston, Texas

BCM neurologists see patients through the Baylor Clinic and some of the world's leading specialty clinics.
Department of Neurology
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Immune Regulation of Autoreactive T Cells

Principal Investigators

Jingwu Zhang, M.D., Ph.D.
Ying C.Q. Zang, M.D., Ph.D.

Summary

Evidence indicates that autoimmune T cells are not completely deleted in the thymus and that they circulate in the periphery and are controlled by various regulatory mechanisms. One of these peripheral regulatory mechanisms involves the idiotypic network. This network regulates the immune responses to both foreign and self-antigens through recognition of the idiotypic determinants of specific antibodies or T cells. Aberrant T cell responses to myelin autoantigens in MS are potentially related to dysregulation of the autoreactive T cells.

Taking advantage of T cell vaccination (where irradiated autoreactive T cells are administered to induce anti-idiotypic regulatory responses), we are seeking to define the distribution pattern and nature of the idiotypic determinants responsible for triggering anti-idiotypic regulation of myelin-reactive T cells. Another regulatory mechanism under investigation by our laboratory is Th1-Th2 cytokine regulatory network. Altered peptide ligand (APL), with analog peptides containing single or multiple alanine substitutions, may also play a role in the attenuation of myelin-reactive T cells. In summary, this part of our MS research is focused on the various regulatory mechanisms that control activation of autoreactive T cells including the idiotypic network, Th1-Th2 cytokine regulation, apoptosis and the altered peptide ligand.

Antigen presentation and activation of MBP-reactive T cells. Attacking points of various therapeutic agents.

Antigen presentation and activation of MBP-reactive T cells. Attacking points of various therapeutic agents.

Blocking of activation of MBP-reactive T cells by altered peptide ligand.

Blocking of activation of MBP-reactive T cells by altered peptide ligand.

Selected References

  1. Zhang, J., Vandevyver, C., Stinissen, P., Meadaer, R. and Raus, J. (1995) In vivo clonotypic regulation of human myelin basic protein-reactive T cells induced by T cell vaccination. Journal of Immunology 155:5868.
  2. Zhang, J., Rivera, V. and Steinman L. (1997) New treatments for multiple sclerosis. In: Current Neurology S. Appel, Ed., IOS Press-Ohmsha; Amsterdam, 17:157.
  3. Zhang, J. (1998) Emerging therapeutic targets in multiple sclerosis: Suppression and elimination of myelin-autoreactive T lymphocytes. Emerging Therapeutic Targets 2:1.
  4. Zang, Y., Kozovska, M., Hong, J., Mann, S., Li, S., Killian, J., Rivera, V. and Zhang, J. (1999) Increased frequency of Fas-sensitive myelin basic protein-reactive T cells in patients with multiple sclerosis. European Journal of Immunology 29:1692.
  5. Zang, Y., Hong, J., Li, S., Killian, J., Rivera, V. and Zhang, J. (2000) Preferential recognition of hypervariable region sequence by anti-idiotypic T cells induced by T cell vaccination in patients with multiple sclerosis. J Immunol. 164:4011.
  6. Hong, J., Zang, Y., Rivera, V., and Zhang, J. (2000) Reactivity and regulatory properties of anti-idiotypic antibodies induced by T cell vaccination in patients with multiple sclerosis. J Immunol. 165:6858.
  7. Zang, Y., Kozovska, M., Li, S., Killian, J., Rivera, V., and Zang, J. (2000) Th2 immune regulation induced by T cell vaccination in patients with multiple sclerosis. Eur J Immunol. 30:908.
  8. Hong, J., Tejada-Simon, M.V., Rivera, V.M., Zang, Y.C.Q., Zhang, J. (2002) Anti-viral properties of interferon beta treatment in patients with multiple sclerosis. Multiple Sclerosis. 8, 237-242.
  9. Salama, H.H., Kolar, O.J., Zang, Y.C.Q., Zhang, J. (2003) Effects of combination therapy of beta-interferon 1a and prednisone on serum immunologic markers in patients with MS. Multiple Sclerosis. 9,28-31.
  10. Zang, Y., Halder, J., Hong, J., Rivera, V., and Zhang J.(2002) Regulatory effects of estriol on T cell migration and cytokine profile: inhibition of transcription factor NF-κB. J. Neuroimmunol. 124, 106-114.
  11. Zang, Y.C.Q., Hong, J., Rivera, V., Killian, J., and Zhang J. (2003) Induction and Reactivity of Human Anti-Idiotypic T Cells Recognizing TCR CDR3 Determinants of Myelin Basic Protein-Reactive T Cells. Interl Immunol. 15,1073-1080.