Baseline viral load and immune activation determine the extent of reconstitution of innate immune effectors in HIV-1-infected subjects undergoing antiretroviral treatment.
We analyzed dendritic cell (DC) and NK cell compartments in relation to CD4 recovery in 21 HIV-infected subjects followed to <50 copies/ml once starting antiretroviral therapy (ART) and observed for 52 wk of sustained suppression. Although CD4 counts increased in all subjects in response to ART, we observed a restoration of functional plasmacytoid DC (PDC) after 52 wk of sustained suppression under ART (from 1850 cells/ml to 4550 cells/ml) to levels comparable to controls (5120 cells/ml) only in subjects with a low baseline viral load, which also rapidly suppressed to <50 copies/ml upon <or=60 days from ART initiation. Recovery of PDC at week 52 correlates with level of CD95 expression on CD8 T cells and PDC frequency following first ART suppression. NK cytotoxic activity increased rapidly upon viral suppression (VS) and correlated with PDC function at week 52. However, restoration of total NK cells was incomplete even after 52 wk on ART (73 cells/mul vs 122 cells/mul in controls). Direct reconstitution experiments indicate that NK cytotoxic activity against virally infected target cells requires DC/NK cooperation, and can be recovered upon sustained VS and recovery of functional PDC (but not myeloid DC) from ART-suppressed subjects. Our data indicate that viremic HIV-infected subjects may have different levels of reconstitution of DC and NK-mediated function following ART, with subjects with lower initial viremia and the greatest reduction of baseline immune activation at VS achieving the greatest level of innate effector cell reconstitution.
Chehimi
Jihed
J
HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA 19104, USA.
Azzoni
Livio
L
Farabaugh
Matthew
M
Creer
Shenoa A
SA
Tomescu
Costin
C
Hancock
Aidan
A
Mackiewicz
Agnes
A
D'Alessandro
Lara
L
Ghanekar
Smita
S
Foulkes
Andrea S
AS
Mounzer
Karam
K
Kostman
Jay
J
Montaner
Luis J
LJ
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology; D020127:Recovery of Function / Q000187:drug effects / Q000276:immunology*; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000276:immunology