Shared alterations in NK cell frequency, phenotype, and function in chronic human immunodeficiency virus and hepatitis C virus infections.
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) cause clinically important persistent infections. The effects of virus persistence on innate immunity, including NK cell responses, and the underlying mechanisms are not fully understood. We examined the frequency, phenotype, and function of peripheral blood CD3- CD56+ NK subsets in HIV+ and HCV+ patients and identified significantly reduced numbers of total NK cells and a striking shift in NK subsets, with a marked decrease in the CD56(dim) cell fraction compared to CD56(bright) cells, in both infections. This shift influenced the phenotype and functional capacity (gamma interferon production, killing) of the total NK pool. In addition, abnormalities in the functional capacity of the CD56(dim) NK subset were observed in HIV+ patients. The shared NK alterations were found to be associated with a significant reduction in serum levels of the innate cytokine interleukin 15 (IL-15). In vitro stimulation with IL-15 rescued NK cells of HIV+ and HCV+ patients from apoptosis and enhanced proliferation and functional activity. We hypothesize that the reduced levels of IL-15 present in the serum during HIV and HCV infections might impact NK cell homeostasis, contributing to the common alterations of the NK pool observed in these unrelated infections.
Meier
Ute-Christiane
UC
The Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berks RG20 7NN, United Kingdom.
Owen
Rachel E
RE
Taylor
Elizabeth
E
Worth
Andrew
A
Naoumov
Nikolai
N
Willberg
Christian
C
Tang
Kwok
K
Newton
Phillipa
P
Pellegrino
Pierre
P
Williams
Ian
I
Klenerman
Paul
P
Borrow
Persephone
P
D017252:CD3 Complex / Q000032:analysis; D019002:CD56 Antigen / Q000032:analysis; D003602:Cytotoxicity, Immunologic; D015658:HIV Infections / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D019409:Interleukin-15 / Q000097:blood; D007694:Killer Cells, Natural / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*
D017252:CD3 Complex; D019002:CD56 Antigen; D019409:Interleukin-15; D007371:Interferon-gamma