CD4^+ T cell-mediated presentation of non-infectious HIV-1 virion antigens to HIV-specific CD8^+ T cells

作     者：XU Jian-qing Franco Lori Julianna Lisziewicz 

作者机构：State Key Laboratory for Infectious Diseases Prevention and Control National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 100050 China Research Institute for Genetic and Human Therapy Washington DC 20007 USA 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2006年第119卷第19期

页      面：1629-1638页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：This study was supported by a grant from the Major Basic Project of China (973) (No. 2005CB522903) 

主　　题：HIV antigen presenting CD4^+ T cell CD8+ T cell immune pathogenesis 

摘      要：Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4^＋ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals. Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens. Results CD4^＋ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8^＋ T cells. Cross presentation required the entry of HIV-1 to CD4^＋ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4^＋ mediated activation of HIV-specific CD8^＋ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses. Contusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4^＋ T cells cross presenting HIV-1 antigen to activate CD8^＋ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1 infection.