Eradication of clonally expanded CD4+ T cells

消除克隆扩增的 CD4 T 细胞

• 批准号: 10621808
• 负责人: JOEL N BLANKSON
• 金额: $ 20.47万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-13 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621808
• 关键词: Acceleration; Anti-Retroviral Agents; Antigens; CD4 Positive T Lymphocytes; Carboplatin; Cell Death; Cell Proliferation; Cells; Cessation of life; Chemotherapy and/or radiation; Clinical; Clonal Expansion; Clone Cells; Cytomegalovirus; DNA; Defective Viruses; Diagnosis; Excision; Frequencies; Future; HIV; HIV Antigens; In Vitro; Individual; Inflammation; Malignant neoplasm of lung; Measures; Modeling; Operative Surgical Procedures; Paclitaxel; Persons; Predisposition; Process; Proliferating; Proviruses; Radiation therapy; Regimen; Residual state; Shock; T-Cell Proliferation; T-Lymphocyte; Testing; Therapeutic; Vaccination; Viral Antigens; Viral Load result; Viral reservoir; Virus; Virus Integration; antiproliferative agents; antiproliferative drugs; antiretroviral therapy; chemoradiation; design; immune activation; integration site; prevent; response

Project Summary Clonal expansion is a process where latently infected CD4+ T cells proliferate in response to their cognate antigen. It is thought that this process contributes significantly to the size of the HIV reservoir and therefore disrupting this mechanism could have a huge impact on the number of latently infected cells. We observed a significant decline in the number of expanded CD4+ T cell clones in an elite suppressor who received chemoradiation for lung cancer and we hypothesize that we can recapitulate this in vitro by stimulating CD4+ T cells with a combination of cognate antigen to induce proliferation, and either chemotherapeutic or antiproliferative agents that would selectively kill the dividing antigen-specific CD4+ T cells. If successful, a two-step process of vaccination of individuals with cognate antigen and short term treatment with chemotherapeutic or antiproliferative agents may be part of a strategy to reduce the size of the reservoir.

项目总结