Cultured blood dendritic cells retain HIV-1 antigen-presenting capacity for memory CTL during progressive HIV-1 infection.
Dendritic cells (DC) are potent APC that may be involved in the pathogenesis of HIV-1 infection. We studied the APC function of DC from HIV-1-infected subjects that were derived from monocyte-depleted PBMC by culture in human IL-4 and human granulocyte-macrophage CSF. The cultured cells from the HIV-1-infected subjects had similar morphology and phenotype of mature DC (CD80 = 41 +/- 8%, CD86 = 77 +/- 5%, CD40 = 87 +/- 6%, CD1a = 1 +/- 1%) to DC cultured from seronegative subjects. The yield of these DC was lower than from HIV-1-seronegative subjects (4 +/- 0% vs 11 +/- 2%, p < 0.01), and the lower DC yields correlated with lower numbers of blood CD4+ T cells (r = 0.60, p < 0.01) and higher plasma viral load (r = -0.49, p < 0.01). DC from HIV-1-infected subjects were infected with recombinant vaccinia virus vectors expressing Gag, Pol, and Env and were able to stimulate equal or higher levels of MHC class I-restricted, anti-HIV-1 memory CTL (CTLm) than were similarly treated, autologous B lymphocyte cell lines. DC pulsed with peptides representing HIV-1 CTL epitopes stimulated higher levels of anti-HIV-1 CTLm responses than did DC infected with the vaccinia virus-HIV-1 constructs. Allogeneic, MHC class I-matched DC also stimulated anti-HIV-1 CTLm activity in cells from HIV-1-infected subjects. DC from early and late stages of HIV-1 infection had a similar ability to activate CTLm specific for targets expressing either HIV-1 genes via vaccinia virus vectors or HIV-1 immunodominant synthetic peptides. However, DC from either early or late stages of HIV-1 infection could not overcome the defect in anti-HIV-1 CTLm response in advanced infection.
Fan
Z
Z
University of Pittsburgh Graduate School of Public Health, PA 15261, USA.
Huang
X L
XL
Zheng
L
L
Wilson
C
C
Borowski
L
L
Liebmann
J
J
Gupta
P
P
Margolick
J
J
Rinaldo
C
C
D000163:Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D000328:Adult; D017951:Antigen Presentation; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D018450:Disease Progression; D015488:HIV Antigens / Q000097:blood* / Q000276:immunology; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000097:blood; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000276:immunology / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology*
D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I; D009842:Oligopeptides