Delayed reconstitution of CD4+ iNKT cells after effective HIV type 1 therapy.
CD1d-restricted natural killer T (iNKT) cells are increasingly recognized as key immunoregulatory cells linking innate and adaptive immunity. These fall into functionally distinct CD4+ versus CD4- subsets that are believed to steer cellular immunity toward tolerigenic/atopic versus proinflammatory phenotypes, respectively. Preferential depletion of the CD4+ subset has been observed in HIV-1 infection, but the repletion of these cells after antiretroviral therapy has not been examined in detail. T lymphocytes, CD8+ lymphocyte activation, viremia, and iNKT cell subsets in peripheral blood were compared between 18 HIV-1-uninfected (Control) and 18 seropositive (SP) men initially not on suppressive antiretroviral therapy. Compared to the Control group, the SP group demonstrated reduction of CD4+ and lesser reduction of CD4- iNKT cells at baseline. After initiation of suppressive antiretroviral treatment, the SP CD4+ iNKT cell levels remained unchanged after a year and increased by 2 years, while CD4+ iNKT cells showed a gradual increase notable after the first year. Over the first year of treatment, there was a significant correlation between changes in total CD4+ T lymphocyte and changes in CD4+ iNKT cell levels, and a significant inverse correlation between changes in CD8+ T lymphocyte activation and changes in CD4- iNKT cell levels. These results confirm preferential depletion of tolerigenic/atopic CD4+ iNKT cells by HIV-1, and suggest that disproportionate persistence of proinflammatory CD4- iNKT cells could contribute to the inappropriate immune activation believed to cause immunodeficiency in HIV-1 infection.
Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA. oyang@mednet.ucla.edu
Otto O
OO
Yang
S Brian
SB
Wilson
Lance E
LE
Hultin
Roger
R
Detels
Patricia M
PM
Hultin
F Javier
FJ
Ibarrondo
Beth D
BD
Jamieson
D044966:Anti-Retroviral Agents / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D012189:Retrospective Studies
D044966:Anti-Retroviral Agents