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

• Published in: Chinese medical journal 2006-10, Vol.119 (19), p.1629-1638
• Main Authors: Xu, Jian-qing, Lori, Franco, Lisziewicz, Julianna
• Format: Article
• Language: English
• Subjects: Adult; Antigen Presentation; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - virology; CD8-Positive T-Lymphocytes - immunology; HIV-1 - immunology; Humans; Lymphocyte Activation; Male; Virion - immunology; 发病机制; 爱滋病病毒; 病毒感染; 被膜抗原
• ISSN: 0366-6999; 2542-5641
• DOI: 10.1097/00029330-200610010-00007

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.