Levels of antigen processing machinery components in dendritic cells generated for vaccination of HIV-1+ subjects.
OBJECTIVE
To evaluate expression of the antigen processing machinery (APM) components and HLA molecules by monocyte-derived dendritic cells (DC) generated from chronically HIV-1 infected subjects on antiretroviral therapy (ART) and to assess their ability to ex vivo induce HIV-1 specific T cells.


METHODS
DC generated in 16 HLA-A2 positive patients were matured in cytokines, pulsed with HIV-1 or other viral peptides and tested in interferon (IFN)-gamma ELISPOT assays. Immature (i)DC, mature (m)DC and viral peptide-pulsed DC were studied by multiparameter quantitative flow cytometry for intracellular APM component expression and for HLA class I and II, beta-2 microglobulin and co-stimulatory molecule surface expression. DC from 13 normal donors served as controls.


RESULTS
Marked heterogeneity in APM component expression levels in iDC and mDC from HIV-1 positive subjects was observed. Nevertheless, the median levels were comparable to those in iDC and mDC, respectively, from normal donors. Patients' mDC pulsed with the HIV-1, influenza A, cytomegalovirus (CMV) or Epstein-Barr virus peptides induced IFN-gamma production by T cells specific for these peptides in ELISPOT assays. The frequency of T cells responsive to influenza A, cytomegalovirus or Epstein-Barr virus peptides was comparable in the patients and normal donors.


CONCLUSIONS
The APM component expression profiles of iDC and mDC were more heterogeneous in subjects with chronic HIV-1 infection on ART, than those in normal donors, although not statistically different. Ex vivo, patients' DC pulsed with HIV-1 peptides induced IFN-gamma production from autologous T cells. Thus, DC obtained from HIV-1 infected subjects on ART were phenotypically and functionally competent.
Connolly
Nancy
N
Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Riddler
Sharon
S
Stanson
Joanna
J
Gooding
William
W
Rinaldo
Charles R
CR
Ferrone
Soldano
S
Whiteside
Theresa L
TL
D016915:AIDS Vaccines / Q000276:immunology*; D000328:Adult; D017951:Antigen Presentation / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D014611:Vaccination
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D018664:Interleukin-12; D007371:Interferon-gamma