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Mechanisms of HSK amelioration

HSK改善机制

基本信息

批准号：
8389553
负责人：
Patrick M Stuart
金额：
$ 35.63万
依托单位：
SAINT LOUIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-01 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8389553
关键词：
Address Antigens Biology Blindness CCL2 gene CCL3 gene CCL4 gene CD28 gene CD4 Positive T Lymphocytes CD80 gene CXCR3 gene Cell surface Cells Cellular Infiltration Cicatrix Clinical Clinical Pathology Comparative Study Cornea Corneal Diseases Country Data Defective Viruses Dendrites Disease Epithelial Experimental Models Eye Generations Genes Glycoproteins Herpesviridae Herpesvirus 1 Herpetic Keratitis Human IL8 gene Immune Immune response Immunotherapy Incidence Infection Inflammation Inflammatory Inflammatory Infiltrate Interleukin-6 Keratitis Keratoplasty Laboratories Lead Macrophage Inflammatory Protein-1 Maintenance Mediating Modeling Molecular Profiling Mus NIH Mouse Pathogenesis Pathology Phenotype Play Proteins Recording of previous events Recurrence Recurrent disease Relative (related person)Reporting Resistance Role Simplexvirus T-Lymphocyte TNFRSF5 gene TNFSF5 gene Testing Therapeutic Intervention Time United States Vaccinated Vaccination Vaccine Therapy Vaccines Viral Viral Antigens Virus Virus Diseases Virus Latency Woman Work base chemokine cytokine design genital herpes human disease improved macrophage neovascularization prevent prophylactic reactivation from latency response success vaccine evaluation virus host interaction

项目摘要

Herpetic stromal keratitis (HSK) is a leading cause of infectious blindness in the United States. Visual loss most commonly results from recurrent stromal disease, as opposed to primary HSK and appears to be the result of immune- mediated corneal destruction. Most experimental models have focused on primary rather than recurrent keratitis. We study a model of recurrent HSK that mimics many clinical and immunological features of recurrent HSK in humans. While current data indicates that primary and recurrent HSK are similar, there are significant differences in the clinical pathology, viral antigen distribution, cellular infiltration within the cornea, importance of both some cytokines and chemokines and responses to vaccine therapy, thus suggesting that the immune responses in these two diseases is not identical. Over the past 15+ years our and a few other labs have characterized much of what is known concerning recurrent HSK. Based on our most recent data concerning the role that costimulatory molecules play in HSK as we have demonstrated the central role that CD28 plays in mediating this disease, but at the same time is involved in suppressing spontaneous viral reactivation from latency. We have also shown that CD137L is likely involved in disease amelioration. These data further support the notion that HSK is mediated by CD4+ cells of the Th1 phenotype and that more importantly, Th2 T cells are strongly associated with less disease. In order to test these hypotheses we will: (1) Determine the role that the proinflammatory molecules IL-6, KC (IL-8), IP10 (CXCL10), and CCL4 play in recurrent HSK disease pathogenesis. (2) Determine the role that co-stimulatory interactions play in both recurrent HSK and in maintenance of viral latency. (3) We will also determine whether therapeutic intervention, either targeting or promoting these interactions, will ameliorate disease using a vaccination paradigm. The information derived from these studies will lead to a better understanding of the biology of recurrent HSK in mice and by extension human disease. Furthermore, these studies could possibly suggest more effective immunotherapies designed to ameliorate human HSK disease.

疱疹性间质角膜炎（HSK）是中国传染性失明的主要原因