In vitro characterization of purified human thymic dendritic cells infected with human immunodeficiency virus type 1.
In the thymus, dendritic cells (DC) are functionally associated with thymocytes and are recognized to play a major role in the intrathymic differentiation of T cells. Several studies have previously investigated the role of DC during HIV-infection, but the status of thymic DC in HIV-1 pathogenesis remains unclear. In this study, we investigated the susceptibility of purified human thymic DC to HIV-1 infection in vitro. HIV-1 was not detected in cell-free supernatants collected from HIV-infected DC. However, these cultures were shown to transmit HIV-1 infection since coculture with permissive MT4 cells resulted in virus production. The exposure of DC in culture to HIV-1 was shown to promote severe DC morphological changes and killing. We also found that one or several heat labile soluble cytotoxic agents present in the HIV-1-infected DC supernatant mediated the killing of thymocytes. Our observations raise the possibility that (1) the HIV-1-induced DC killing, (2) the capacity of DC to transmit viral infection, and/or (3) the release of HIV-1-mediated cytotoxic agent(s) from DC may contribute to AIDS pathogenesis in vivo.
Beaulieu
S
S
Départment de microbiologie et immunologie, Faculté de médecine, Université de Montréal, Québec, Canada.
Kessous
A
A
Landry
D
D
Montplaisir
S
S
Bergeron
D
D
Cohen
E A
EA
D000818:Animals; D016923:Cell Death; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity*; D006801:Humans; D017403:In Situ Hybridization; D055646:Killer Factors, Yeast; D011506:Proteins / Q000276:immunology / Q000378:metabolism; D012367:RNA, Viral / Q000032:analysis; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology*
D055646:Killer Factors, Yeast; D011506:Proteins; D012367:RNA, Viral