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Reduced Expression of Siglec-7, NKG2A and CD57 on Terminally Differentiated CD56-CD16+ NK Cell Subset is associated with NK Cell Dysfunction in Chronic HIV-1 clade C Infection.

Reduced Expression of Siglec-7, NKG2A and CD57 on Terminally Differentiated CD56-CD16+ NK Cell Subset is associated with NK Cell Dysfunction in Chronic HIV-1 clade C Infection.
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Zulu M, Naidoo K, Mncube Z, Jaggernath M, Goulder PJ, Ndung'u T, Altfeld M, Thobakgale CF,


Zulu M, Naidoo K, Mncube Z, Jaggernath M, Goulder PJ, Ndung'u T, Altfeld M, Thobakgale CF, (click to view)

Zulu M, Naidoo K, Mncube Z, Jaggernath M, Goulder PJ, Ndung'u T, Altfeld M, Thobakgale CF,

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AIDS research and human retroviruses 2017 08 16() doi 10.1089/AID.2017.0095

Abstract
BACKGROUND
HIV-1 viremia has been shown to induce several phenotypic and functional abnormalities in natural killer (NK) cells. To assess immune defects associated with HIV viremia, we examined NK cell function, differentiation status and phenotypic alterations based on expression of inhibitory and activating receptors on NK cells in HIV-1 subtype C chronically infected participants from Durban, South Africa.

METHODS
NK cell phenotypic profiles were characterized by assessing Siglec-7, NKG2A and NKG2C markers on frozen peripheral blood mononuclear cells (PBMCs) from viremic, antiretroviral therapy (ART)-naïve HIV-1 chronically infected participants (n=23), HIV-1 chronically infected participants who have been on combination antiretroviral therapy (cART) for at least 12 months (n=23) compared to healthy donors (n=23). NK cell differentiation was assessed by measurement of KIR and NKG2A expression; and CD57 and CD107a measurements were carried out in HIV viremic and healthy donors. All phenotypic and functional assessments were analyzed using multicolour flow cytometry.

RESULTS
HIV-1 infected participants displayed greater frequencies of the CD56-CD16+ (CD56negative) NK cell subset compared to healthy donors (p<0.0001). Down-regulation of Siglec-7 and NKG2A and up-regulation of NKG2C was more pronounced in the CD56negative NK cell subset of viremic participants. The CD56negative subset demonstrated a differentiated (KIR+NKG2A-) phenotype with reduced CD57 expression and lower degranulation capacity in HIV-1 infected participants compared to healthy donors. CONCLUSION
HIV-1 infection induces the expansion of the CD56negative NK cell subset marked by altered receptor expression profiles that are indicative of impaired function and may explain the overall NK cell dysfunction observed in chronic HIV-1 infection.

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