BONE-MARROW-DERIVED DENDRITIC CELLS, INFECTION WITH HUMAN-IMMUNODEFICIENCY-VIRUS, AND IMMUNOPATHOLOGY

Dendritic cells (DC) exposed to HIV-I show nonproductive infection tha t 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 transm ission, Carriage of virus and viral antigen by DC into lymph nodes may allow clustering and activation of T cells and production of protecti ve immune responses. However, secondary infection of activated T cells from infected DC could cause dissemination of virus and loss of infec ted DC and T cells. In asymptomatic infection, fewer dendritic cells w ith reduced capacity to stimulate CD4 T cell proliferation are found b efore evidence of T cell abnormalities, and these early changes in ant igen-presenting cel:ls may result in a decline in the production of CD 4 memory T cells. However, DC fuel ongoing production of antibody to H IV-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 ce lls within the thymus may affect maturation and contribute to loss of the ''naive'' T cell population. Further loss of memory T cells may oc cur through syncytium formation with infected DC. Finally, in AIDS pat ients, there is a failure in the development and the function of DC fr om CD34(+) stem cells. In conclusion, the infection of dendritic cells , loss in their numbers, and changed signaling to T cells may shape th e pattern of immunity, during infection with HIV-1. Conversely, treatm ents that reverse the defect in antigen presentation by DC may improve cell-mediated immunity.