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.
Departments of Microbiology, New York University School of Medicine, New York, NY 10016, USA.
Aimee
A
El Hed
Alka
A
Khaitan
Lina
L
Kozhaya
Nicolas
N
Manel
Demetre
D
Daskalakis
William
W
Borkowsky
Fred
F
Valentine
Dan R
DR
Littman
Derya
D
Unutmaz
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