CD4 T cell respnse to Human herpesvirus-6

CD4 T 细胞对人类疱疹病毒 6 的反应

• 批准号: 9226033
• 负责人: Lawrence J. Stern
• 金额: $ 47.69万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9226033
• 关键词: Acute; Antiviral Agents; Autoimmune Diseases; Autoimmune thyroiditis; Biochemical; Biological Assay; Blood Cells; Bone Marrow Suppression; CD4 Positive T Lymphocytes; Cell Line; Cessation of life; Characteristics; Child; Childhood; Chronic; Clinical; Collaborations; Complication; Cytomegalovirus; Data; Diagnosis; Diagnostic; Encephalitis; Epitopes; Exanthema Subitum; Febrile Convulsions; Goals; Hospitalization; Human; Human Herpesvirus 4; Human Herpesvirus 6; Immune; Immune response; Immunocompetent; Immunosuppression; Infection; Infectious Agent; Interleukin-10; Interleukin-2; Kidney Transplantation; Life; MHC Class II Genes; Mediating; Medical; Memory; Molecular; Mus; National Institute of Allergy and Infectious Disease; Natural Killer Cells; Nature; Neurologic; Organ; Organ Transplantation; Pathology; Patients; Pattern; Population; Primary Infection; Process; Proteins; Pulmonary Inflammation; Reagent; Regulation; Reporting; Role; Sampling; Solid; Stem cells; System; T cell regulation; T cell response; T memory cell; T-Lymphocyte; T-Lymphocyte Epitopes; Techniques; Testing; Therapeutic immunosuppression; Transplant Recipients; Transplantation; Vaccination; Viral; Virus; Virus Diseases; Work; antiviral immunity; base; clinical development; cognitive function; cross reactivity; cytokine; early childhood; experience; experimental study; immunosuppressed; improved; multiple sclerosis patient; novel; pathogen; peripheral blood; reactivation from latency; response; seropositive; tool

This project is a comprehensive look into the CD4 T cell response to human herpesvirus 6 (HHV-6), an emergent / re-emergent human pathogen. In most people infection in childhood resolves uneventfully to a chronic life-long infection held in check by cellular immune responses. However, viral reactivation after immunosuppression can cause serious illness, neurological complications, and even death, and is an important complication following organ transplantation. One aim of the project is to characterize memory T cell responses to this chronic infection, and compare them to responses to acute infection. CD4 and CDS T cell responses to HHV-6 will be characterized in healthy immune donors and also in kidney transplant recipients experiencing viral reactivation. A possible role for IL-10 in regulating these responses will be investigated. These analysis will involve ex vivo analysis of, peripheral blood and primary cell lines, using functional assays and newly-developed class II MHC oligomers, and will be pursued in collaboration with project 2, which is investigating analogous CD4 T cell functional subsets in mice. A second aim of the project is to understand the role of NK cells in regulating T cell responses to HHV-6. Preliminary data indicate that NK populations present in peripheral blood regulate CD4 T cells responding to HHV-6. Several mechanistic hypotheses will be explored using ex vivo analysis of human peripheral blood and primary cell lines. This work will be pursued in collaboration with project 1, which is investigating similar NK phenomenon in other systems. A third aim of the project is to investigate and functionally characterize CD4 T cell responses to HHV-6 that are cross-reactive with other viruses. Several recently identified HHV-6 T cell epitopes are similar to those from other common viral infections. Based on principles established in previous work on CDS cross-reactivity patterns, we predict that the HHV-6 specific CD4 T cell response can recognize heterologous infection by other viruses including EBV, CMV, and lAV. This prediction will be tested using ex vivo analysis of human peripheral blood and primary cell lines, and biochemical and structural analysis of MHC and TCR proteins. This aim will be pursued in collaboration with project 3.

该项目全面研究了CD4 T细胞对人类疱疹病毒6 （HHV-6）的反应