Escape of monocyte-derived dendritic cells of HIV-1 infected individuals from natural killer cell-mediated lysis.
OBJECTIVE
To verify whether the in vitro sensitivity of immature dendritic cells (iDC) to lysis by autologous natural killer (NK) cells from HIV-infected individuals might be correlated with HIV disease progression.


METHODS
Both dendritic cells (DC) and interlekin (IL)-2 activated NK cells were obtained from 13 HIV-infected individuals early after seroconversion and not receiving highly active antiretroviral therapy (HAART) and from 14 individuals with chronic HIV infection under HAART. The rate of NK cell-mediated killing of autologous iDC was correlated with classical parameters of HIV evolution.


METHODS
Peripheral blood monocytes obtained from the Ficoll-derived leukocyte fraction after adherence to plastic were stimulated with granulocyte-macrophage colony stimulating factor plus IL-4 to induce their differentiation into iDC to be used as target cells in a standard 4-h cytotoxicity assay. A fraction of autologous leukocytes was stimulated with IL-2 to induce activation of NK cells to be used as effector cells.


RESULTS
During early HIV infection the extent of ex vivo lysis of monocyte-derived DC by activated autologous NK cells was inversely and directly correlated with the levels of viraemia and with the percentage of circulating CD4 T cells, respectively. In contrast, the capacity of NK cells to kill iDC was lost independently of the levels of plasma viraemia or the concurrence of HAART in chronically infected individuals. Addition of exogenous HIV Tat during the cytotoxicity assay inhibited NK cell-mediated lysis of DC.


CONCLUSIONS
NK cell-mediated immune surveillance against infected DC may be effective only during early HIV infection and may not be restored by HAART.
Laboratory of Clinical Immunology, Department of Immunology and Infectious Diseases, San Raffaele Scientific Institute, Diagnostica e Ricerca San Raffaele s.p.a., Milan, Italy.
Silvana
S
Tasca
Giuseppe
G
Tambussi
Silvia
S
Nozza
Brunella
B
Capiluppi
Maria Raffaella
MR
Zocchi
Laura
L
Soldini
Fabrizio
F
Veglia
Guido
G
Poli
Adriano
A
Lazzarin
Claudio
C
Fortis
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D005260:Female; D015696:Gene Products, tat / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1; D006801:Humans; D007108:Immune Tolerance; D007694:Killer Cells, Natural / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D019562:Viral Load; D014766:Viremia / Q000276:immunology; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus; D016178:Granulocyte-Macrophage Colony-Stimulating Factor