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| Research Interests |
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| T-cells and cytokines in infectious disease, particularly Leishmania. |
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| Research Summary |
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Dr. Scott’s current research is focused on understanding the development, regulation and maintenance of CD4+ Th1 and Th2 cells in order to design new vaccines and immunotherapies for infectious diseases. The laboratory primarily focuses on experimental  murine infections with the protozoan parasite, Leishmania, which provides a well-characterized model of T helper cell differentiation. The use of IL-12 as an adjuvant to promote Th1 cell development, as well as the ability of combined drug and IL-12 therapy to promote a Th2 to Th1 switch, was first shown in this laboratory. Both findings have implications for the control and treatment of infectious diseases, autoimmunity and allergy. While much has been learned about the development of Th1 cells, our understanding of how to maintain Th1 responses–or cell-mediated immunity–is limited. This is highlighted by the fact that there is no vaccine for human leishmaniasis. Dr. Scott’s laboratory is investigating the role of cytokines, antigen-dose, CD8+ T cells and antigen persistence in the development of immunologic memory. These studies indicate that a population of lymph node homing memory T cells, which have been called central memory T cells, are generated during Leishmania infection, and can be maintained in the absence of parasites. Future studies are directed at determining how to increase this population of memory T cells following vaccination. In related experiments, this laboratory has demonstrated that a Leishmania mutant, which lacks phosphoglycans and fails to induce disease, is maintained in vivo and protects mice against challenge with virulent organisms. Studies are in progress to characterize the immunity induced by these mutant parasites. Finally, studies are ongoing to understand how different species of Leishmania influence T helper cell subset development. While L. major induces a Th1 response and a healing infection in many strains of mice, the same strains of mice infected with parasites belonging to the L. mexicana complex fail to develop a Th1 response or heal. Thus, the laboratory is focused on defining the parasite virulence factors that modulate T helper cell development by different species of Leishmania.
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| Selected Publications : Search PubMed for articles |
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Scott, P., P. Natovitz, R.L. Coffman, E. Pearce and A. Sher. 1988. Immunoregulation of cutaneous leishmaniasis. T cell lines that transfer protective immunity or exacerbation belong to different T helper subsets and respond to distinct parasite antigens. Journal of Experimental Medicine. 168:1675-1684. Afonso, L. C. C., Scharton, T. S., Vieira, L. Q., Wysocka, M., Trinchieri, G., and P. Scott. 1994. The adjuvant effect of Interleukin 12 in a vaccine against Leishmania major. Science. 263:235-237. Nabors, G.S., L.C.C. Afonso, J.P. Farrell, and P. Scott. 1995. A switch from a Th2 to Th1 type response and cure of established Leishmania major infection in mice is induced by combined therapy with Interleukin-12 and Pentostam. Proceedings of the National Academy of Science USA. 92:3142-3146. Park, A.Y. B.D. Hondowitz, M. Kopf and P. Scott. 2002. The role of IL-12 in maintaining resistance to Leishmania major. Journal of Immunology 168:5771-5777. Zaph, C., and P. Scott. 2003. Th1 cell-mediated resistance to cutaneous infection with Leishmania major is independent of P- and E-selectins. Journal of Immunology 171:4726-4732. Lemos, M.P., F. Esquivel, P. Scott, and T.M. Laufer. 2004. MHC Class II expression restricted to CD8a+ and CD11b+ dendritic cells is sufficient for control of Leishmania major. Journal of Experimental Medicine. 199:725-730. Uzonna, J.E., G.F. Spath, S.M. Beverley, and P. Scott. 2004. Vaccination with phosphoglycan deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response. Journal of Immunology. 172:3793-7. Artis, D., L. M. Johnson, K. Joyce, C. Saris, A. Villarino, C. A. Hunter, and P. Scott. 2004. Cutting Edge: Early IL-4 production governs the requirement for IL-27/WSX-1 signaling in the development of protective Th1 cytokine responses following Leishmania major infection. Journal of Immunology 172:4672-5. Uzonna, J.E., K. Joyce, and P. Scott. 2004 Low dose Leishmania major promotes a transient T helper cell type 2 response that is downregulated by interferon- producing CD8+ T cells. Journal of Experimental Medicine. 199:1559-1566. Zaph, C., J. Uzonna, S. M. Beverley and P. Scott. 2004. Central memory T cells mediate long-term immunity to Leishmania major in the absence of persistent parasites. Nature Medicine 10:1104-1110. |
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