The major objective of this proposal is to investigate the role that cytotoxic lymphocytes play in the pathogenesis of Herpes simplex virus type 1 (HSV-1) corneal lesions and to use this information in an attempt to intervene in the infectious process through manipulation of the cytotoxic response. Our preliminary observations suggest that such intervention may be feasible. The studies contained in this proposal will achieve three major goals. First, the cytotoxic activity that develps in the PBL following topical corneal (TC), intracameral (IC), and footpad (FP) infection with HSV-1 will be further characterized with regard to: (l) the involvement of interferon (IFN) in the early activation of non-specific cytoxic activity in PBL, (2) the infection, and (3) the capacity of in vitro HSV-1 stimulation to augment the cytotoxic activity of PBL. These studies will utilize a standard IFN assay to quantitate IFN in serum and culture supernatants, and a standard chromium release assay to measure cytotoxic activity against HSV-1 infected class I MHC compatible and incompatible targets and YAC-1 (NK-sensitive) targets. The cytotoxic activity that develops in RLN cells following IC, TC, and FP HSV-1 infection will be further characterized. The involvement of IFN, IL-2, and other soluble factors in the HSV-1 stimulated augmentation of cytotoxic activity will be tested. The mechanism by which the cytotoxic activity of RLN cells from IC infected mice is suppressed will also be investigated. These studies will involve in vitro lymphocyte subpopulation depletion, mixing experiments, and assays for the detection of soluble suppressor factors in culture supernatants of HSV-1 stimulated RLN(IC) cells, as well as in vivo experiments involving splenectomy and adoptive transfer. The information gained in the first two section of the proposed studies will then be used in an attempt to intervene in the HSV-1 infectious process through manipulation of the cytotoxic response. The studies in this section will: (l1) determine the involvement of IC infection-induced suppressor cells in the protection against corneal lesions afforded to TC-infected mice by simultaneous IC infection, (2) determine the involvement of cytotoxic lymphocytes in the pathogenesis of herpetic corneal lesions, and (3) determine the role of PBL NK cells in protection against corneal lesions.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY005945-01A1
Application #
3261678
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1986-09-30
Project End
1989-09-29
Budget Start
1986-09-30
Budget End
1987-09-29
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Schools of Medicine
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
Jeon, Sohyun; Rowe, Alexander M; Carroll, Kate L et al. (2018) PD-L1/B7-H1 Inhibits Viral Clearance by Macrophages in HSV-1-Infected Corneas. J Immunol 200:3711-3719
Rowe, Alexander M; Yun, Hongmin; Hendricks, Robert L (2017) Exposure Stress Induces Reversible Corneal Graft Opacity in Recipients With Herpes Simplex Virus-1 Infections. Invest Ophthalmol Vis Sci 58:35-41
Rowe, Alexander M; Yun, Hongming; Treat, Benjamin R et al. (2017) Subclinical Herpes Simplex Virus Type 1 Infections Provide Site-Specific Resistance to an Unrelated Pathogen. J Immunol 198:1706-1717
Yun, Hongmin; Lathrop, Kira L; Hendricks, Robert L (2016) A Central Role for Sympathetic Nerves in Herpes Stromal Keratitis in Mice. Invest Ophthalmol Vis Sci 57:1749-56
Kuffova, Lucia; Knickelbein, Jared E; Yu, Tian et al. (2016) High-Risk Corneal Graft Rejection in the Setting of Previous Corneal Herpes Simplex Virus (HSV)-1 Infection. Invest Ophthalmol Vis Sci 57:1578-87
Buela, Kristine-Ann G; Hendricks, Robert L (2015) Cornea-infiltrating and lymph node dendritic cells contribute to CD4+ T cell expansion after herpes simplex virus-1 ocular infection. J Immunol 194:379-87
Jeon, Sohyun; St Leger, Anthony J; Cherpes, Thomas L et al. (2013) PD-L1/B7-H1 regulates the survival but not the function of CD8+ T cells in herpes simplex virus type 1 latently infected trigeminal ganglia. J Immunol 190:6277-86
St Leger, Anthony J; Jeon, Sohyun; Hendricks, Robert L (2013) Broadening the repertoire of functional herpes simplex virus type 1-specific CD8+ T cells reduces viral reactivation from latency in sensory ganglia. J Immunol 191:2258-65
Rowe, A M; St Leger, A J; Jeon, S et al. (2013) Herpes keratitis. Prog Retin Eye Res 32:88-101
Kinchington, Paul R; Leger, Anthony J St; Guedon, Jean-Marc G et al. (2012) Herpes simplex virus and varicella zoster virus, the house guests who never leave. Herpesviridae 3:5

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