Robert L. Hendricks, PhD
Joseph F. Novak Endowed Chair
Professor and Vice-Chair for Research
Director, Ophthalmology & Visual Sciences Research Center
Departments of Ophthalmology, Immunology, Microbiology and Molecular Genetics and Biochemistry
University of Pittsburgh School of Medicine
Kate Carroll (Graduate Student)
Moira Geary (Research Technician)
Jared E. Knickelbein, MD/ PhD (Resident/ Fellow)
Alexander Rowe, PhD (Postdoctoral Research Associate)
Hongmin Yun MD, PhD (Research Associate)
Dr. Hendricks’ research focuses on three important aspects of the immune response to herpes simplex virus type 1 (HSV-1):
HSV-1 induces immunopathology in the cornea of the eye that can lead to scarring and blindness. CD4 T cells through Th1 and Th17 cytokines mediate the inflammation in HSV-1 infected mouse corneas, providing an interesting and clinically important model for studying mechanisms of T cell-mediated inflammation and tissue destruction. The clarity of the corneal tissue permits direct observation of the developing inflammation, and the cornea facilitates manipulation of the T cell-antigen presenting cell interaction and local cytokine and chemokine functions, the focus of current studies.
When corneas become scarred by recurrent bouts of HSV-1 induced inflammation the only recourse is corneal transplantation. Unfortunately patients with recurrent HSV-1 corneal disease reject transplanted corneas at a very high rate. Our laboratory is employing a model of corneal transplantation in mice to study the mechanisms of accelerated corneal graft rejection in mice with previous HSV-1 corneal disease.
During primary infection at mucosal surfaces, HSV-1 invades sensory neurons, is transported to neuronal cell bodies in the sensory ganglia, and there establishes a latent (quiescent) infection. Reactivation from latency results in recurrent disease in innervated tissues including the cornea. Our laboratory first demonstrated that CD8 T cells provide active immunesurveillance of latently infected neurons, preventing reactivation from the latent state. We are currently characterizing T cell receptor specificity and function of CD8 T cells in latently infected sensory ganglia with the goal of developing vaccines or other means of augmenting their protective function.
Select Recent Publications
- St. Leger, A.J., Peters, B., Sidney, J., Sette, A., and Hendricks, R.L.:Defining the herpes simplex virus-specific CD8+ T cell repertoire in C57BL/6 mice. J. Immunol. 186: 3927-3933, 2011
- Frank, G. M., A. J. Lepisto, M. L. Freeman, B. S. Sheridan, T. L. Cherpes, and R. L. Hendricks. 2010. Early CD4(+) T cell help prevents partial CD8(+) T cell exhaustion and promotes maintenance of Herpes Simplex Virus 1 latency. J.Immunol. 184:277-286.
- Sheridan, B. S., T. L. Cherpes, J. Urban, P. Kalinski, and R. L. Hendricks. 2009. Reevaluating the CD8 T-cell response to herpes simplex virus type 1: involvement of CD8 T cells reactive to subdominant epitopes. J.Virol. 83:2237-2245. PMC 2643732
- Knickelbein, J. E., K. M. Khanna, M. B. Yee, C. J. Baty, P. R. Kinchington, and R. L. Hendricks. 2008. Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science 322:268-271. PMC 2680315
- Cherpes, T. L., J. L. Busch, B. S. Sheridan, S. A. Harvey, and R. L. Hendricks. 2008. Medroxyprogesterone acetate inhibits CD8+ T cell viral-specific effector function and induces herpes simplex virus type 1 reactivation. J.Immunol. 181:969-975. PMC 2553693
- Freeman, M. L., B. S. Sheridan, R. H. Bonneau, and R. L. Hendricks. 2007. Psychological stress compromises CD8+ T cell control of latent herpes simplex virus type 1 infections. J.Immunol. 179:322-328. PMC 2367250
- Sheridan, B. S., K. M. Khanna, G. M. Frank, and R. L. Hendricks. 2006. Latent virus influences the generation and maintenance of CD8+ T cell memory. J.Immunol. 177:8356-8364. PMC 2366996
- Decman, V., P. R. Kinchington, S. A. Harvey, and R. L. Hendricks. 2005. Gamma interferon can block herpes simplex virus type 1 reactivation from latency, even in the presence of late gene expression. J.Virol. 79:10339-10347. PMC 1182646
- Xu, M., A. J. Lepisto, and R. L. Hendricks. 2004. CD154 signaling regulates the Th1 response to herpes simplex virus-1 and inflammation in infected corneas. J.Immunol. 173:1232-1239.
- Khanna, K. M., R. H. Bonneau, P. R. Kinchington, and R. L. Hendricks. 2003. Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. Immunity 18:593-603.
Robert L. Hendricks, PhD
EEI-919, 203 Lothrop St.
Pittsburgh, PA 15213