Phenotypic and functional characteristics of HIV-specific CD8 T cells and gag sequence variability after autologous dendritic cells based therapeutic vaccine.
A decrease in HIV-1 specific CD8 T-cell responses associated with a partial control of viral replication occurred in 12 HIV-1-infected patients during autologous dendritic cells vaccination. HIV CD8 T cells were detected in 6/10 patients during immunizations, increasing after HAART discontinuation in 3 of them. Tet+ CD8 cells mainly had an effector phenotype (CD45RA-/+ CCR7- and CD28- and Perf+/-) and maintained IFN-gamma release throughout follow-up. By contrast, patients with CD45RA-/+ CCR7+ Perf+ HIV-specific cells showed a decrease in peptide-specific IFN-gamma production during vaccinations while levels were recovered when off HAART. No major mutations in either Gag p24 and p17 immunodominant epitopes were observed that might have explained the impaired CD8+ T-cell responses. Taken together, heterogeneity in the maturation status of HIV-specific CD8 T cells may be partially involved in the drop of peptide-specific IFN-gamma production during immunizations.
López
Anna
A
Retrovirology and Viral Immunopathology Laboratory, Hospital Clínic, University of Barcelona, Barcelona, Spain.
van der Lubbe
Nils
N
Sánchez-Palomino
Sonsoles
S
Arnedo
Mireia
M
Nomdedeu
Meritxell
M
Castro
Pedro
P
Guilà
Meritxell
M
Maleno
Maria J
MJ
García
Felipe
F
Gallart
Teresa
T
Gatell
José M
JM
Plana
Montserrat
M
D016915:AIDS Vaccines / Q000276:immunology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology*; D015488:HIV Antigens / Q000235:genetics*; D016655:HIV Core Protein p24 / Q000235:genetics; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D010641:Phenotype; D020539:Sequence Analysis, Protein; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D016915:AIDS Vaccines; D015488:HIV Antigens; D016655:HIV Core Protein p24; D006680:HLA Antigens; D016056:Immunodominant Epitopes; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D007371:Interferon-gamma