ROLE OF MEMORY T CELL DYNAMICS IN SIV INFECTION

记忆 T 细胞动力学在 SIV 感染中的作用

• 批准号: 7958422
• 负责人: Louis J. Picker
• 金额: $ 16.53万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958422
• 关键词: Cells; Chronic; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Disease; Failure; Funding; Grant; Immune; Immunologic Deficiency Syndromes; Infection; Institution; Link; Macaca mulatta; Maintenance; Mediating; Memory; Pattern; Population; Primates; Research; Research Personnel; Resources; Role; SIV; Site; Source; T memory cell; T-Cell Proliferation; United States National Institutes of Health; Viral; Work; memory CD4 T lymphocyte

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our work has provided compelling evidence that the onset of immune deficiency in pathogenic SIVmac239 infection of rhesus macaques (RM) is intimately linked with patterns of CD4+ memory T cell dynamics, and reflects a complex interplay of direct viral cytopathogenicity and the indirect effects of persistent immune activation on CD4+ memory T cell proliferation, differentiation and survival. Our data have strongly implicated a decline in effector site, CD4+ effector memory (TEM) populations below a crucial threshold as a major proximate mechanism of overt immunodeficiency, but significantly, have also demonstrated that in CCR5-tropic SIV infection, even massive viral-mediated destruction of CD4+ TEM is rarely, if ever, sufficient for functional failure of this population. Instead, our data indicate that this failure is determined in large part by the ability of CD4+ central memory T cells (TCM) to produce new TEM, which in turn depends on the maintenance of the CD4+ TCM population itself. In chronic SIV infection, we found that a slow decline of the number and often, proliferative activity of CD4+ TCM underlies CD4+ TEM population failure, and "sets the clock" for the onset of overt disease.

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们的工作提供了令人信服的证据表明，致病性SIVmac 239感染恒河猴（RM）的免疫缺陷的发病与CD 4+记忆T细胞动力学模式密切相关，并反映了直接病毒致细胞病变性和持续免疫激活对CD 4+记忆T细胞增殖，分化和存活的间接影响的复杂相互作用。 我们的数据强烈暗示了效应位点的下降，CD 4+效应记忆（TEM）群体低于一个关键阈值，作为明显免疫缺陷的一个主要的近似机制，但重要的是，也证明了在CCR 5嗜性SIV感染，即使是大规模的病毒介导的CD 4 + TEM的破坏很少，如果有的话，足以使这个群体的功能衰竭。 相反，我们的数据表明，这种失败在很大程度上是由CD 4+中央记忆T细胞（TCM）产生新的TEM的能力决定的，这反过来又取决于CD 4 + TCM群体本身的维持。 在慢性SIV感染中，我们发现CD 4 + TCM的数量和增殖活性的缓慢下降是CD 4 + TEM群体失败的基础，并为明显疾病的发作“设置时钟”。