CD8+ T cell effectors against microsporidia

对抗微孢子虫的 CD8 T 细胞效应

基本信息

批准号：
8532815
负责人：
IMTIAZ AHMED KHAN
金额：
$ 37.53万
依托单位：
GEORGE WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-17 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8532815
关键词：
AIDS/HIV problem Acquired Immunodeficiency Syndrome Adopted Albendazole Animals Biological Assay Blood Body Weight decreased CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cell Communication Cells Child Clinical Data Defect Development Diagnosis Diarrhea Effector Cell Elderly Encephalitozoon cuniculi Encephalitozoon hellem Enterocytozoon bieneusi Exhibits Generations Geographic Locations Goals HIV HIV Infections Hand Heterogeneity Human Immune Immune response Immunity Immunocompromised Host Immunotherapeutic agent Impairment Individual Infection Kinetics Knock-out Laboratories Lead Link Maintenance Mediating Memory Methods Microsporidia Microsporidiosis Modeling Mono-S Mus Opportunistic Infections Organ Transplantation Organism Parasite Control Parasites Patients Persons Pharmaceutical Preparations Play Population Population Study Predisposition Prevalence Production Risk Role Septata intestinalis Source Symptoms System Systemic disease T cell response T-Lymphocyte T-Lymphocyte Subsets Testing Therapeutic Transplant Recipients Vaccines Viral adaptive immunity base cytokine fumagillin improved interest novel therapeutic intervention oral infection pathogen perforin public health relevance response socioeconomics

项目摘要

DESCRIPTION (provided by applicant): Microsporidial infection continues to be a problem for HIV infected individuals and are associated as a cause of persistent diarrhea and systemic disease in these people. Recent studies have also implicated these agents in causing illness to HIV- negative groups like travelers and immuno-competent elderly individuals. The limited studies available with Encephalitozoon cuniculi, a microsporidia that can be easily cultured in the laboratory have demonstrated importance of T cells in protection against the parasite. Amongst the T cell subsets, CD8+ T lymphocytes are primary effector cells responsible for protective immunity with CD4+ and ?¿ T playing an important helper role. Knock out animals lacking either of the two subsets exhibit sub-optimal CD8+ T cell immunity to E.cuniculi infection. Recent studies from our laboratory suggest that IL- 21, a cytokine produced by both CD4 and ?¿ T cells, is important for the induction of multifunctional CD8+T cell response against the pathogen. Neutralization of IL-21 response leads to decreased polyfunctional and increased mono-functional CD8+ T cell response as a result of which they are less protective and the host is unable to clear infection in an efficient manner. Importance of poly or multifunctional CD8+ T cells has recently been associated with increased protection against viral pathogens, although the direct link has yet to established. Thus it appears that IL-21 mediated polyfunctional CD8+ T cell response is key to protection against E.cuniculi infection which poses a risk to HIV infected population. The proposal comprises of three specific aims. In the first specific aim the kinetics o IL-21 response by ?¿ and CD4+ T cell population in response to E.cuniculi infection will be evaluated. The mechanism of IL-21 production and priming of CD8+ T cell response against the pathogen will be assayed. In the second specific aim role of IL-21 in the development of polyfunctional CD8+ T cell effector response will be determined. Further, importance of polyfunctionality in the development of robust long-term response will be analyzed. In the third and final specific aim various strategies which can lead to induction and maintenance of polyfunctional CD8+ T cell response in immunocompromised (like HIV-infected) host will be tested and therapeutic role of IL-21 in this situation will be evaluated. These studies will have fr reaching implications in other opportunistic infections and viral pathogens where development of robust CD8+ T cell response is critical for host protection.

描述（通过应用程序证明）：在这些人和免疫能力的老年人中，微观物质侵蚀仍然是腹泻和全身性疾病。。 t在我们的实验室中扮演重要的研究。 T细胞，多功能CD8+ T细胞反应的t-Cells对病原体的响应，并增加了单官能CD8+ T细胞反应，因此较少的保护和宿主无法清除效率直接链接尚未建立的响应。 CD4+ T细胞群体对E.Cuniculi的响应将评估IL-21的产生机理，而CD8+ T细胞反应Ag的启动将在病原体中分析IL-21的第二个特定目标。多功能CD8+ T细胞效应器进一步恢复。将对HIV感染的宿主进行测试，并在其他其他病毒病原体中评估IL-21的治疗作用。