TY - JOUR
T1 - Cultured Blood Dendritic Cells Retain HIV-1 Antigen-Presenting Capacity for Memory CTL during Progressive HIV-1 Infection
AU - Fan, Zheng
AU - Huang, Xiao Li
AU - Zheng, Lian
AU - Wilson, Cara
AU - Borowski, Luann
AU - Liebmann, James
AU - Gupta, Phalguni
AU - Margolick, Joseph
AU - Rinaldo, Charles
PY - 1997/11/15
Y1 - 1997/11/15
N2 - 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.
AB - 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.
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M3 - Article
C2 - 9366424
AN - SCOPUS:0031573052
SN - 0022-1767
VL - 159
SP - 4973
EP - 4982
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -