Susceptibility of human Th17 cells to human immunodeficiency virus and their perturbation during infection.
BACKGROUND
Identification of the Th17 T cell subset as important mediators of host defense and pathology prompted us to determine their susceptibility to human immunodeficiency virus (HIV) infection.


RESULTS
We found that a sizeable portion of Th17 cells express HIV coreceptor CCR5 and produce very low levels of CCR5 ligands macrophage inflammatory protein (MIP)-1alpha and MIP-1beta. Accordingly, CCR5(+) Th17 cells were efficiently infected with CCR5-tropic HIV and were depleted during viral replication in vitro. Remarkably, HIV-infected individuals receiving treatment had significantly reduced Th17 cell counts, compared with HIV-uninfected subjects, regardless of viral load or CD4 cell count, whereas treatment-naive subjects had normal levels. However, there was a preferential reduction in CCR5(+) T cells that were also CCR6 positive, which is expressed on all Th17 cells, compared with CCR6(-)CCR5(+) cells, in both treated and untreated HIV-infected subjects. This observation suggests preferential targeting of CCR6(+)CCR5(+) Th17 cells by CCR5-tropic viruses in vivo. Th17 cell levels also inversely correlated with activated CD4(+) T cells in HIV-infected individuals who are receiving treatment.


CONCLUSIONS
Our findings suggest a complex perturbation of Th17 subsets during the course of HIV disease potentially through both direct viral infection and virus indirect mechanisms, such as immune activation.
El Hed
Aimee
A
Departments of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Khaitan
Alka
A
Kozhaya
Lina
L
Manel
Nicolas
N
Daskalakis
Demetre
D
Borkowsky
William
W
Valentine
Fred
F
Littman
Dan R
DR
Unutmaz
Derya
D
D044966:Anti-Retroviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D054405:Chemokine CCL3 / Q000096:biosynthesis; D054407:Chemokine CCL4 / Q000096:biosynthesis; D004198:Disease Susceptibility; D005434:Flow Cytometry; D006678:HIV / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D019409:Interleukin-15 / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000097:blood; D008213:Lymphocyte Activation / Q000276:immunology; D016133:Polymerase Chain Reaction; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000097:blood*; D054399:Receptors, CCR6 / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000821:virology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000821:virology*; D019562:Viral Load
D044966:Anti-Retroviral Agents; C106311:CCR6 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019409:Interleukin-15; D020381:Interleukin-17; D019713:Receptors, CCR5; D054399:Receptors, CCR6; D007371:Interferon-gamma