The number and function of circulating dendritic cells may limit effector memory CD4+ T-cell responses in HIV patients responding to antiretroviral therapy.
Some HIV patients who previously experienced severe immunodeficiency retain low pathogen-specific T-cell responses despite a virological response to antiretroviral therapy (ART). To identify correlates with dysfunction in accessory cell populations, HIV patients were stratified into groups maintaining high or low CD4(+) T-cell IFN-gamma responses to cytomegalovirus (CMV) over 4-8 years on ART. Myeloid dendritic cells (mDC), plasmacytoid (p) DC, M-DC8(+) cells and monocytes were enumerated and mRNA of cytokines and activation molecules were quantitated in purified subpopulations. Proportions of pDC were lower (p=0.043) and mDC were higher (p=0.043) in low responders. TRAIL receptor 2 (DR5) mRNA levels in pDC (p=0.0008) and mDC (p=0.0062) were lower in high responders compared to controls. Levels of IL-15 mRNA were higher in mDC from high responders (p=0.015) and levels of IL-10 mRNA were higher in M-DC8(+) cells from low responders (p=0.036). Hence CMV-specific CD4(+) T-cell IFN-gamma responses may be affected by numbers and function of circulating DC.
Department of Clinical Immunology and Immunogenetics, Royal Perth Hospital, Perth, Australia. sonia.fernandez@uwa.edu.au
Sonia
S
Fernandez
Shelley F
SF
Stone
Patricia
P
Price
Martyn A
MA
French
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002452:Cell Count; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006678:HIV; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D037182:T-Cell Antigen Receptor Specificity
D019380:Anti-HIV Agents; D016207:Cytokines; D012333:RNA, Messenger; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D007371:Interferon-gamma