Lucille P. Markey Charitable Trust

sponsor of

Basic and Clinical Research Career Tracks in Internal Medicine at

Columbia-Presbyterian Medical Center

Research Interests

My research interest is to study the regulation of peripheral immune responses; especially the immuno-regulatory pathway mediated by the Qa-1 restricted regulatory CD8+ T cells.

Research Activities

The essential function of immune system is to mount effective immune responses to virtually any foreign antigens while avoiding harmful immune responses to self. How the immune system maintains tolerance to self while achieving affinity maturation to foreign in the periphery is one of the most important and fundamental questions in both basic and clinical immunology. We have been testing a new and unique idea that Qa-1 restricted regulatory CD8+ T cells maintain self-tolerance and facilitate affinity maturation of TCR repertoire to foreign antigens by selectively down regulating T cells with intermediate affinity to both self and foreign antigens. The hypothesis is based on a pathway of immunoregulation mediated by Qa-1 restricted regulatory CD8+ T cells that we have defined during the past few years (reviewed in Annu. Rev. Immunol. 18:185, 2000). We have provided evidence that the Qa-1 restricted CD8+ T cells play an important role in regulating immune responses to both self and foreign antigens by selectively down-regulating certain but not all antigen activated T cells. The molecular interaction between the regulatory CD8+ T cells and target CD4+ T cells is through the recognition of Qa-1/self-peptide/s expressed on certain activated CD4+ T cells by the aB TCR on regulatory CD8+ T cells. We also provided evidence that CD8+ T cells control the MBP reactive TCR repertoire by selectively down-regulating T cell clones with higher growth potential responding to MBP, which are enriched in potentially pathogenic self-reactive T cell clones in EAE. We thus proposed an “affinity model of peripheral T cell regulation” as a potential mechanism of selective down-regulation of certain antigen activated CD4+ T cells by the Qa-1 restricted regulatory CD8+ T cells. We hypothesized that only T cells bearing TCRs of intermediate affinity, to both self and foreign antigens, will process and present Qa-1/self-peptide/s as a consequence of the initial cognitive encounter between the particular TCR expressed by CD4+ T cells and the MHC class II/peptide complex presented on antigen presenting cells. Only the T cells expressing Qa-1/self-peptide/s on their surface are subject to the down-regulation by the Qa-1 restricted regulatory CD8+ T cells.

If the hypothesis is proven correct, it will not only be a conceptual leap forward toward the understanding of the biology of Qa-1 restricted regulatory CD8+ T cell mediated immuno-regulatory pathway, but also a new dimension added to our current understanding of the peripheral regulation of the immune system. We envision that there will also be huge potential application of this pathway in therapeutic approaches based on our understanding of the basic mechanisms by which the immune system could be manipulated to specifically suppress or enhance certain immune responses in auto-immune disease, organ transplantation, immunity against infectious disease and tumor immunology.

We have established several animal models to study the biological function of the regulatory pathway mediated by the Qa-1 restricted CD+ T cells in responses to both self and foreign antigens. This include immune responses to HEL in both wild type and HEL transgenic mice, the Experimental Autoimmune Encephalomyelitis (EAE) model in B10PL mice and type 1 diabetes (T1D) in NOD mice.

Selected Publications

Jiang, H., Zhang, S-L., and Pernis, B. 1992. Role of CD8+ T cells in murine experimental allergic encephalomyelitis. Science 256:1213-1215.

Jiang, H., Ware, R., Stall, A., Flaherty, L., Chess, L., and Pernis, B. 1995. Murine CD8+ T Cells that Specifically Delete Autologous CD4+ T Cells Expressing V?8 TCR: A Role of the Qa-1 Molecule. Immunity 2:185-194.

Jiang, H., Kashleva, H., Xu, L., Forman, J., Flaherty, L., Pernis, B., Braunstein, N. and Chess, L. 1998. T Cell Vaccination Induces TCR V? Specific, Qa-1 Restricted Regulatory CD8+T cells. PNAS, 95: 4533-4537.

Jiang, H., Chess, L. 2000. The Specific Regulation of Immune Responses by CD8+ T Cells Restricted by the MHC Class Ib Molecule, Qa-1. Annual Review of Immunol. 18:185-216.

Jiang, H., Braunstein, N., Yu, B., Winchester, R., and Chess, L. 2001. CD8+ T Cells Control the TH Phenotype of MBP Reactive CD4+ T Cells in EAE Mice. PNAS. 98: 6301-6306.

Shi Du, Yan, Wu, Zhi-Ying, Zhang, Hui Ping, Furtado, Glacia, Brown, Chris Stern, Alan, LaFaille, Juan, Chess, Leonard, Stern, David M. and Jiang, Hong. 2003. Suppression of Experimental Autoimmune Encephalitis by Selective Blockade of Encephalitogenic T-Cell Infiltration of The Central Nervous System. Nature Medicine. 9:287.

Jiang, H. , S. Curran, E. Ruiz-Vazquez, B. Liang, R. Winchester, L. Chess. 2003. Regulatory CD8+ T cells Fine Tune the MBP Reactive T Cell Receptor V? Repertoire during EAE. PNAS, 100(14):8378-8383.

Jiang, H., Chess, L. 2003. An Integrated Model of Immunoregulation Mediated by Regulatory T Cell Subsets. Advances in Immunology. In Press