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Predominance of Th1 cells in ocular tissues during herpetic stromal keratitis
1Department of Microbiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37996-0845.
Insights
Herpetic stromal keratitis (HSK) involves CD4+ T cells. Ocular lymphocytes in active HSK exhibit a Th1 cytokine profile, suggesting their role in corneal immunopathology.
Area of Science:
- Immunology
- Ophthalmology
- Virology
Background:
- Herpetic stromal keratitis (HSK) is an immunopathologic condition of the eye caused by HSV-1.
- CD4+ T cells are implicated in HSK pathogenesis, but their specific immunopathologic role remains unclear.
Purpose of the Study:
- To investigate the cytokine profile of inflammatory cells from eyes with active HSK.
- To determine the T helper cell subset involved in mediating HSK.
Main Methods:
- Isolation of inflammatory cells from eyes during active HSK.
- In vitro culture and stimulation of cells with antigen (Ag) or mitogens.
- Cytokine analysis (IL-2, IFN-gamma, TNF-alpha/beta, IL-4, IL-10, IL-1) using stimulated cells.
Main Results:
- Inflammatory cells included polymorphonuclear leukocytes, macrophages, and CD4+ lymphocytes.
- Stimulated ocular lymphocytes produced IL-2, IFN-gamma, and TNF-alpha/beta, but not IL-4 or IL-10.
- Ocular cells stimulated with PMA produced IL-1, identifying lymphocytes as Th1 cells.
Conclusions:
- Ocular lymphocytes in active HSK are predominantly Th1 cells.
- Th1 cells may contribute to corneal tissue damage in HSK through their cytokine production.
- The findings suggest mechanisms for Th1 cell accumulation and tissue damage in the eye during HSK.
Abstract:
Herpetic stromal keratitis (HSK) appears to represent an immunopathologic response in the cornea of the eye to HSV-1. T cells of the CD4+ subset were shown to be involved in the mediation of HSK, but how they subserve an immunopathologic role is uncertain. In the present report, we have isolated cells from eyes in the active phase of HSK and studied their cytokine profile after culture in vitro or stimulation with Ag or nonspecific mitogens. Inflammatory cells recovered from eyes consist of polymorphonuclear leukocytes, macrophages, and lymphocytes. As reported before, all the lymphocyte recovered were of the CD4+ phenotype. After stimulation in vitro with Ag or mitogen the cytokines IL-2, IFN-gamma, and TNF-alpha/beta were produced, but not the cytokines IL-4 and IL-10. Thus, on the basis of cytokine profile, ocular lymphocytes were identified as Th1 cells. Ocular cells were also stimulated with PMA and shown to produce IL-1. The results were discussed in terms of the possible means by which the Th1 cells induce tissue damage in HSK as well as in terms of the possible means by which a preferential accumulation of Th1 cell occurs in the eye.