Department Affiliation: Primary: Pharmacology and Molecular Sciences
Degree: DVM/Ph.D., Faculty of Veterinary Medicine,
University of Berne
Rank: Assistant Professor
Telephone Number: 410-502-4424
Fax Number: 410-955-3023
E-mail address: sstager1@jhmi.edu
School of Medicine Address: Room 655 Broadway Research Building, 733 N. Broadway, Baltimore, MD 21205
Immunoparasitology; CD8+ T-cells; Leishmania; vaccination
The main interest of the laboratory lies in the immunology of Leishmaina donovani infections, focusing on CD8+ T-cell biology. L.donovani is the causative agent of Visceral Leishmaniasis (VL), with 500 000 new cases reported each year. We study VL not only as it is an elegant model of chronic infectious diseases, but also to gain a greater understanding of the immune response to the parasite. This knowledge may eventually help us better design vaccine strategies or other therapeutical interventions.
Two aspects of CD8+ T-cell biology are investigated:
- The development of CD8+ T-cell responses in the experimental model of Visceral Leishmaniasis (VL);
- The requirements for vaccine-induced CD8+ T-cell responses.
Several studies have now demonstrated the importance of CD8+ T-cells in the murine model of VL. Depletion of CD8+ T-cells during the chronic stage of infection leads to an increased parasite burden in target organs, the liver and the spleen. Furthermore, adoptive transfer of activated antigen-specific CD8+ T-cells during chronic Leishmania donovani infections dramatically reduces parasite burden within 2 days. However, little is known about how CD8+ T-cell responses develop, or the function, the state of activation, and antigen-specificity of these cells during infection. In order to answer these questions, an OVA- transgenic L.donovani system has been generated. This system will allow us to study antigen-specific CD8+ T- cell responses, giving special consideration to early priming events, requirements for activation, and expansion during experimental VL, as a model of chronic infectious diseases.
CD8+ T-cells are not only important effector cells during L.donovani infections, they also play a key role following vaccination with the recombinant protein HASPB1, a L. donovani surface protein. Investigations into the mechanisms of protection induced by rHASB1 immunization revealed a strict requirement for IL-4 during the very early priming events, and uncovered a new pathway for CD8+ T-cell activation. This new pathway involves complement and natural antibodies, which provide the intrinsic adjuvant effect necessary for priming of HASPB1-specific CD8+ T-cells. The laboratory aims to study the role of IL-4 in the induction of HASPB1-specific CD8+ T-cells, the cellular requirements, and the role of complement and natural antibodies during the early priming events.
Representative Publications:
- Polley, R.*, Stäger, S.*, Prickett, S., Maroof, A., Zubairi, S., Smith, D.F., and Kaye, P.M. Adoptive immunotherapy against experimental visceral leishmaniasis with CD8+ T-cells requires the presence of cognate antigen, Infection and Immunity, 74 (1):773-776. *Both authors contributed equally. Pub Med Reference
- Kaye, P.M., Svensson, M., Ato, M., Maroof, A., Polley, R., Stäger, S., Zubairi, S., and Engwerda, C.R. The immunopathology of experimental visceral leishmaniasis, Immunological Reviews 201:239-253, 2004. Pub Med Reference
- Stäger, S. and Kaye, P.M. CD8+ T cell priming regulated by cytokines of the innate immune system, Trends in Molecular Medicine 10:366-371, 2004. Pub Med Reference
- Engwerda, C.R., Ato, M., Stäger, S., Alexander C., and Kaye, P.M. Distinct roles for lymphotoxin-alpah and TNF-alpha in the control of Leishmania donovani infection, American Journal of Pathology, 165:2123-2133, 2004. Pub Med Reference
- Stäger, S., Alexander J., Kirby A.C., Botto M., Van Rooijen N., Smith D.F., Brombacher, F., and Kaye, P.M. Natural antibodies and complement are endogenous adjuvants for vaccine-induced CD8+ T cell responses, Nature Medicine 9:1287-1292, 2003. Pub Med Reference
- Ato, M., Stäger, S., Engwerda, C.R. and Kaye, P.M. Defective CCR7-dependent migration of dendritic cells contributes to the development of chronic visceral leishmaniasis, Nature Immunology 3:1185-1191, 2002. Pub Med Reference
- Stäger, S., Smith, D.F., and Kaye, P.M. Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis, Journal of Immunology 165:7064-7071, 2000. Pub Med Reference
Other graduate programs in which Dr. Stäger participates:
