Monocyte-derived dendritic cells from HIV type 1-infected individuals show reduced ability to stimulate T cells and have altered production of interleukin (IL)-12 and IL-10.
Monocyte-derived dendritic cells (MDDCs) have been used in therapeutic vaccination for cancer. A small number of studies have employed a similar approach to vaccinate human immunodeficiency virus (HIV)-infected individuals. We have thus analyzed the functional properties of MDDCs generated from HIV-infected individuals who either are receiving highly active antiretroviral therapy or are therapy naive. There was no difference in the MDDC phenotype or efficiency of MDDC generation between HIV-infected individuals and healthy control subjects. Despite this, the MDDCs derived from both groups of infected individuals were severely impaired in their ability to stimulate the proliferation of allogeneic T cells. Furthermore, production of interferon-gamma was reduced in T cells stimulated by MDDCs. These functional changes may be at least partly explained by reduced interleukin-12 and increased interleukin-10 secretion on stimulation with lipopolysaccharide and CD40 ligand. Our findings suggest that MDDCs used in therapeutic vaccination of HIV-infected individuals may show reduced potency.
Department of Immunology, Faculty of Medicine, Imperial College, and Department of HIV/GU Medicine, Chelsea and Westminster Hospital, London, United Kingdom.
Sandrine
S
Buisson
Adel
A
Benlahrech
Brian
B
Gazzard
Frances
F
Gotch
Peter
P
Kelleher
Steven
S
Patterson
D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D053762:Interleukin-12 Subunit p40 / Q000096:biosynthesis*; D009000:Monocytes / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*
D019380:Anti-HIV Agents; D053762:Interleukin-12 Subunit p40; D012333:RNA, Messenger; D016753:Interleukin-10