Bone marrow-derived dendritic cells, infection with human immunodeficiency virus, and immunopathology.
Dendritic cells (DC) exposed to HIV-1 show nonproductive infection that may become productive as they mature. The distribution of DC within genital mucosa and their susceptibility to infection particularly with clade E viruses could be reflected in the ease of heterosexual transmission. Carriage of virus and viral antigen by DC into lymph nodes may allow clustering and activation of T cells and production of protective immune responses. However, secondary infection of activated T cells from infected DC could cause dissemination of virus and loss of infected DC and T cells. In asymptomatic infection, fewer dendritic cells with reduced capacity to stimulate CD4 T cell proliferation are found before evidence of T cell abnormalities, and these early changes in antigen-presenting cells may result in a decline in the production of CD4 memory T cells. However, DC fuel ongoing production of antibody to HIV-1. Signaling by DC to T cells may thus underlie two major features of early HIV infection--loss in CD4+ memory T cells and persistence of antibody production. In AIDS, infected dendritic and epithelial cells within the thymus may affect maturation and contribute to loss of the "naive" T cell population. Further loss of memory T cells may occur through syncytium formation with infected DC. Finally, in AIDS patients, there is a failure in the development and the function of DC from CD34+ stem cells. In conclusion, the infection of dendritic cells, loss in their numbers, and changed signaling to T cells may shape the pattern of immunity during infection with HIV-1. Conversely, treatments that reverse the defect in antigen presentation by DC may improve cell-mediated immunity.
Knight
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SC
Antigen Presentation Research Group, Imperial College School of Medicine at Northwick Park Institute for Medical Research, Harrow, Middlesex, United Kingdom.
Patterson
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D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001853:Bone Marrow / Q000276:immunology* / Q000473:pathology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D015658:HIV Infections / Q000276:immunology* / Q000473:pathology* / Q000628:therapy; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D006801:Humans; D018664:Interleukin-12 / Q000627:therapeutic use; D008221:Lymphoid Tissue / Q000276:immunology / Q000473:pathology; D015398:Signal Transduction; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018664:Interleukin-12; D015215:Zidovudine