Altered distribution of natural killer cell subsets identified by CD56, CD27 and CD70 in primary and chronic human immunodeficiency virus-1 infection.
Human natural killer (NK) (CD3- CD56+) cells can be divided into two functionally distinct subsets, CD3- CD56(dim) and CD3- CD56(bright). We analysed the distribution of NK cell subsets in primary and chronic human immunodeficiency virus-1 (HIV-1) infection, to determine if HIV infection stage may influence the subset distribution. In primary infection, contrary to chronic infection, the CD3- CD56(dim) subset was expanded compared to healthy controls. We also studied the effect of antiretroviral therapy administered early in infection and found that NK cell subset distribution was partially restored after 6 months of antiretroviral therapy in primary infection, but not normalized. Recently, NK cells have been divided into CD27- and CD27+ subsets with different migratory and functional capacity and CD27-mediated NK cell activation has been described in mice. We therefore investigated whether CD27 and/or CD70 (CD27 ligand) expression on NK cells, and thus the distribution of these novel NK subsets, was altered in HIV-1-infected patients. We found up-regulated expression of both CD27 and CD70 on NK cells of patients, resulting in higher proportions of CD27(high) and CD70(high) NK cells, and this phenomenon was more pronounced in chronic infection. Experiments conducted in vitro suggest that the high interleukin-7 levels found during HIV-1 infection may participate in up-regulation of CD70 on NK cell subsets. Imbalance of NK cell subsets and up-regulated expression of CD27 and CD70 initiated early in HIV-1 infection may indicate NK cell activation and intrinsic defects initiated by HIV-1 to disarm the innate immune response to the virus.
Titanji
Kehmia
K
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Sammicheli
Stefano
S
De Milito
Angelo
A
Mantegani
Paola
P
Fortis
Claudio
C
Berg
Louise
L
Kärre
Klas
K
Travi
Giovanna
G
Tassandin
Chiara
C
Lopalco
Lucia
L
Rethi
Bence
B
Tambussi
Giuseppe
G
Chiodi
Francesca
F
D053282:CD27 Ligand / Q000097:blood; D018791:CD4 Lymphocyte Count; D019002:CD56 Antigen / Q000097:blood; D002478:Cells, Cultured; D002908:Chronic Disease; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D016131:Lymphocyte Subsets / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood; D015854:Up-Regulation / Q000276:immunology
D053282:CD27 Ligand; D019002:CD56 Antigen; C505771:CD70 protein, human; D015851:Interleukin-7; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7