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


CONCLUSIONS
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.
Xu
Jian-qing
JQ
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. jianqingxu@chinaaids.cn
Lori
Franco
F
Lisziewicz
Julianna
J
D000328:Adult; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D014771:Virion / Q000276:immunology*