Abnormal presence of semimature dendritic cells that induce regulatory T cells in HIV-infected subjects.
Dendritic cells (DCs), because they orchestrate the immune response to microbes, represent an ideal target for pathogens attempting to evade the immune system. We hypothesized that interactions between human immunodeficiency virus (HIV) and DCs lead to the development of a semimature state, in which DCs migrate to lymph nodes but induce tolerance in T cells, rather than immunity. We found that lymph nodes from untreated HIV-infected subjects contained an abundance of semimature DCs, the disappearance of which correlated with the initiation of highly active antiretroviral therapy (HAART). Such lymph nodes also contained an abundance of T cells that had a regulatory phenotype and that persisted after HAART. Lymph node DCs from untreated HIV-infected subjects cultured with normal allogeneic T cells induced these T cells to adopt the phenotype of regulatory T cells, an ability that was lost after HAART. We conclude that HIV infection correlates with the presence of semimature DCs that stimulate T cell tolerance rather than immunity. These regulatory T cells may contribute to the lack of effective HIV immune responses.
Krathwohl
Mitchell D
MD
Department of Medicine, University of Minnesota, Minneapolis, USA. mitch@rosettastonelabs.com.
Schacker
Timothy W
TW
Anderson
Jodi L
JL
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
D019380:Anti-HIV Agents