CD4 T cells and anti-viral control in SIV infection

SIV 感染中的 CD4 T 细胞和抗病毒控制

基本信息

批准号：
7167875
负责人：
Joseph John Mattapallil
金额：
$ 16.2万
依托单位：
HENRY M. JACKSON FDN FOR THE ADV MIL/MED
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-02-01 至 2009-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7167875
关键词：
Acquired Immunodeficiency Syndrome Acute Animal Model Animals Anti-Retroviral Agents Antigens Antiviral Response Autologous Biological Assay Biological Preservation Blood CD4 Positive T Lymphocytes CD8B1 gene Cell Count Cell Cycle Kinetics Cell Differentiation process Cells Clinical Color Coupled Disease Evolution Exhibits Flow Cytometry Frequencies Gagging Generations HIV Highly Active Antiretroviral Therapy Hour Immune response Immune system Immunological Models Individual Infection Infection Control Interleukin-2 Lead Longevity Lymphocytic choriomeningitis virus Macaca mulatta Maintenance Measures Mediating Mesentery Modeling Molecular Mucous Membrane Mus Natural regeneration Nature Outcome Peptides Peripheral Phase Play Principal Investigator Proliferating Research Personnel Reverse Transcriptase Polymerase Chain Reaction Role SIV Sampling Shapes Simplexvirus Sorting - Cell Movement Staining method Stains Subfamily lentivirinae Symptoms Syndrome T-Lymphocyte T-Lymphocyte Subsets TNFRSF5 gene TNFRSF6 gene TNFSF5 gene Techniques Therapeutic Tissue Preservation Tissues Viral Viral Load result Viremia Virus Diseases Week base insight jejunum lymph nodes memory CD4 T lymphocyte pathogen peptide V pinacolyl methylphosphonic acid pol genes prevent programs response virus pathogenesis

项目摘要

DESCRIPTION (provided by applicant): HIV infection is characterized by an extensive loss of CD4 T cells very early during infection. This coupled with the demonstration that HIV specific CD4 T cell are preferentially infected and destroyed during the course of HIV infection suggests that the ability of the immune system to generate anti-viral immune responses to control HIV is severely compromised very early during HIV infection. Recent studies in small animal modes and HIV infected subjects treated with anti-retroviral therapy (ART) during primary infection indicate that early loss of CD4 T cells may have significant implications for the generation and maintenance of anti-viral CDS T cell responses. The exact role of CD4 T cells in CDS mediated control of HIV infection has not been completely delineated. The long term objectives of this study are to delineate the role of CD4 T cell help in the generation of anti-viral immune responses, and to determine how these responses correlate with durable control of infection and long term outcome. The Specific Aims of this proposal are (1) to determine if early initiation of ART can preserve CD4 T cells in peripheral and mucosal tissues, and if this preservation correlates with qualitative changes in the nature of anti-viral CDS T cell responses (2) to examine if the qualitative differences in the nature of CDS T cell responses correlate with durable viral control and favorable long term outcome after cessation of ART. We hypothesize that early ART will preserve CD4 T cells that in turn will lead to generation of stronger and more effective poly functional CDS T cell responses that will aid in better control of viral infection. Rhesus macaques infected with SIVmac239 and treated with PMPA and FTC will be used in this study. The degree of CD4 T cell preservation in both peripheral and mucosal tissues after ART will be determined using multi-color flow cytometry and molecular techniques. SIV specific CDS T cell responses will be evaluated by measuring multiple functional markers simultaneously using intracellular staining and multi-color flow cytometry. These studies will provide extremely valuable insights into the role of CD4 T cells in CDS mediated control of HIV infection, and will help develop better therapeutic approaches for durable control of HIV infection.

描述（由申请人提供）：艾滋病毒感染的特征是在感染过程中很早就丧失了CD4 T细胞。结合以下证明，在HIV感染过程中，HIV特异性CD4 T细胞优先被感染和破坏，这表明免疫系统在HIV感染期间很早就严重损害了免疫系统对控制HIV的抗病毒免疫反应的能力。在原发性感染期间，在接受抗逆转录病毒治疗（ART）治疗的小动物模式和艾滋病毒感染受试者中的最新研究表明，CD4 T细胞的早期丧失可能对抗病毒CDS T细胞反应的产生和维持可能具有重要意义。 CD4 T细胞在CDS介导的HIV感染的控制中的确切作用尚未完全描述。这项研究的长期目标是描述CD4 T细胞在产生抗病毒免疫反应中的作用，并确定这些反应与感染和长期结局的持久控制如何相关。该提案的具体目的是（1）确定艺术的早期开始是否可以保留外周和粘膜组织中的CD4 T细胞，以及该保存是否与抗病毒CDS T细胞反应性质的质量变化相关（2），以检查CDS T细胞在CDS T细胞性质上是否与持久性的术语相关，并在持久的术语中是否具有良好的术语和术语相关。我们假设早期ART将保留CD4 T细胞，而CD4 T细胞反过来会导致产生更强大，更有效的多功能CDS T细胞反应，从而有助于更好地控制病毒感染。本研究将使用感染SIVMAC239并用PMPA和FTC处理的恒河猕猴。使用多色流式细胞仪和分子技术，将确定ART后外周血和粘膜组织中CD4 T细胞的保存程度。 SIV特异性CD T细胞反应将通过使用细胞内染色和多色流式细胞仪同时测量多个功能标记来评估。这些研究将提供对CD4 T细胞在CDS介导的HIV感染控制中的作用的极为宝贵的见解，并将有助于开发更好的治疗方法，以持久控制HIV感染。