Stephen Jennings

Stephen Jennings

Professor, Microbiology and Immunology

Ph.D., 1982, University of Melbourne, Melbourne, Australia

245 N. 15th Street
Philadelphia, PA 19102
Tel: 215-762-4139
Fax: 215-762-7784
Email: Stephen.Jennings@drexelmed.edu

Research Staff: Manxin Zhang, Ph.D.
Graduate Students: Christina Kollias, Sharon Bandstra

Keywords:

CD8+ T cells; Herpes simplex virus; dendritic cells; cytokines; CTL; neuroinvasion

Research Interests

Our laboratory is interested in the immunological basis for the control of infection and pathology associated with complex viral pathogens. Our principal focus has been HSV-1, which infects mucocutaneous epithelial cells and sensory neurons, and causes a lifelong latent infection in the nervous system. Our current focus is the role of the innate and acquired immune responses involved in resisting HSV-1 infection, and how these two components of immunity interact with each other to generate optimal protective responses.

Analysis of HSV-1-specific CD8+ T cell responses. We have focused upon the events resulting in a potent, protective CD8+ T cell response against cutaneous HSV-1 infections. We have defined the kinetics of CD8+ T cell activation and the acquisition of effector function by this subpopulation. We know that two subpopulations of HSV-1-specific CD8+ T cells are generated during the initial response to infection: one expressing high levels of CD25 (IL-2 receptor α-chain); and a second population expressing low levels of CD25. Our current studies are investigating the relative contribution of each subpopulation to the control of infection in the skin and nervous system, their relationship to each other, the role of IL-2 and IL-15 in their development, and the contribution of each to long-term HSV-1-specific CD8+ T cell memory.

Analysis of the immunological basis for resistance to cutaneous HSV-1 infection. Similar to human patients infected with HSV-1 and/or HSV-2, inbred mouse strains exhibit a spectrum of susceptibility to cutaneous HSV infection. The ability to resist cutaneous HSV-1 is associated with rapid synthesis of type I IFNs (IFN-α/β) and early activation of natural killer (NK) cells, and viral clearance is dependent upon HSV-1-specific T cells. Our recent studies have focused upon the role of dendritic cells (DCs) in the intrinsic resistance to HSV-1 and determined that DCs are crucial for preventing lethal infection of the central nervous system. We are currently working on the hypothesis that certain DC subpopulations synthesize high levels of type I IFNs, which in turn activate NK cells and T cells to optimal activity. We are also investigating the role of particular HSV-1 genes to determine their role in HSV-1-mediated impairment of DC function in vivo. Finally, we are attempting to map precisely the genetic loci associated with innate resistance to HSV-1, using congenic strains of mice derived from naturally resistant and sensitive mouse strains.

Selected Research Publications

McNally, J. M., Andersen, H. A., Chervenak, R., and S. R. Jennings. Phenotypic characteristics associated with the acquisition of HSV-specific CD8 T-lymphocyte-mediated cytolytic function in vitro. Cell. Immunol., 194: 103-111, 1999.
McNally, J. M., Dempsey, D., Wolcott, R. M., Chervenak, R., and S. R. Jennings. Phenotypic identification of antigen-dependent and antigen-independent CD8 CTL precursors in the draining lymph node during acute cutaneous herpes simplex virus type 1 infection. J. Immunol., 163: 675-681, 1999.
Jones, C. M., Cose, S. C., McNally, J. M., Jennings, S. R., Heath, W. R., and F. R. Carbone. Diminished secondary CTL response in draining lymph nodes on cutaneous challenge with herpes simplex virus. J. Gen. Virol., 81: 407-414, 2000.
Zhang, Y. F., Smith, P. M., Jennings, S. R., and D. J. O’Callaghan. Determination of specific antibody-secreting cells following immunization with EHV-1 KyA and recombinant glycoprotein D by ELISPOT in CBA mice. Virology 268: 482-492, 2000.
Andersen, H., Dempsey, D., Chervenak, R., and S. R. Jennings. Expression of intracellular interferon-g in HSV-1-specific CD8-positive T cells identifies distinct responding subpopulations during the primary response to infection. J. Immunol., 165: 2101-2107, 2000.
Kawachi, S., Morise, Z., Jennings, S., Conner, E., Cockrell, A., Laroux, F. S., Chervenak, R. Wolcott, M., van der Heyde, H., Gray, L., Feng, L., Granger, N., Specian, R. D., and M. B. Grisham. Cytokine and adhesion molecule expression in SCID mice reconstituted with CD4+ T cells. Inflamm. Bowel Dis., 6: 171-180, 2000.
Smith, P. M., Zhang, Y. F., Grafton, W. D., Jennings, S. R., and D. J. O’Callaghan. Severe immunopathology in the murine lung elicited by the pathogenic EHV-1 strain RacL11 correlates with the early production of MIP-1a, MIP-1b, MIP-2 and TNF-a. J. Virol., 74: 10034-10040, 2000.
Vallien, G., Langley, R., Jennings, S. R., Specian, R., and D. N. Granger. Expression of endothelial cell adhesion molecules in neovascularized tissue. Microcirculation, 7: 249-258, 2000.
Oshima, T., Laroux, F. S., Coe, L. L., Morise, Z., Kawachi, S., Bauer, P., Grisham, M. B., Specian, R. D., Carter, P., Jennings, S. R., Granger, D. N., Joh, T., and J. S. Alexander. Interferon-gamma and interleukin-10 reciprocally regulate endothelial junction integrity and barrier function. Microvasc. Res., 61: 130-143, 2000.
Zhang, Y., Smith, P. M., Frampton, A. R., Osterrieder, N., Jennings, S. R., and D. J. O'Callaghan. Cytokine Profiles and Long Term Virus-Specific Antibodies following Immunization of CBA Mice with Equine Herpesvirus 1 and Viral Glycoprotein D. Viral Immunol., 16: 307-320, 2003.
Kassim, S. H., Rajasagi, N. K., Zhao, X., Chervenak, R., and S. R. Jennings. In vivo ablation of CD11c-positive dendritic cells increases susceptibility to HSV-1 infection and hampers the NK and T cell responses. J. Virol., 80: 3985-3993, 2006.
Jain, P., Ahuja, J., Khan, Z. K., Shimzu, S., Meucci, O., Kampani, K., Jennings, S. R., and B. Wighdahl. Modulation of dendritic cell maturation and functions by the Tax protein of human T cell leukemia virus type 1: implications for viral neuropathogenesis. J. Leukocyte Biol., 82: 44-56, 2007.
Borowski, A. B., Boesteanu, A. C., Mueller, Y. M., Carafides, C., Topham, D. J., Altman, J. D., Jennings, S. R., and P. D., Katsikis. Memory CD8+ T cells require CD28 costimulation. J. Immunol., 179(10): 6494-6503, 2007.