Antibody-dependent CD56 T cell responses are functionally impaired in long-term HIV-1 infectionReportar como inadecuado

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, 13:76

First Online: 04 November 2016Received: 29 July 2016Accepted: 30 October 2016


BackgroundAntibody-dependent cellular cytotoxicity ADCC, which mainly mediated by natural killer NK cells, may play a critical role in slowing human immunodeficiency virus type-1 HIV-1 disease progression and protecting from HIV-1 infection. Besides classic NK cells, CD56+ T cells also have some NK cell-like properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells. However, little is known about the potentials of antibody-dependent CD56+ T cell responses and the association between antibody-dependent CD56+ T cell responses and HIV-1 disease progression.

ResultsIn the present study, we showed evidences that, in addition to NK cells, CD56+ T cells could generate degranulation upon CD16 cross-linking. Ex vivo study showed that FcγRIII CD16-mediated CD56+ T cell responses were distinctly induced by IgG antibody-bound P815 cells. Comparatively, CD56− T cells and invariant NKT CD3+ 6B11+ failed to induce antibody-dependent activation. Antibody-dependent CD56+ T cell responses were mainly ascribed to CD4-CD8 double negative subset and were functionally impaired in long-term HIV-1-infected former plasma donors, regardless of hepatitis C virus HCV coinfection status. Also, CD56+ T cell-mediated HIV-1-specific antibody-dependent responses were declined in men who have sex with men with HIV-1 infection over 3 years. Finally, we showed that matrix metalloprotease MMP inhibitor GM6001 could partially restored antibody-dependent CD56+ T cell responses of chronic HIV-1-infected subjects.

ConclusionsOur results suggested that CD56+ T cells could mediate ADCC responses and the responses were impaired in chronic HIV-1 infection.

KeywordsCD56+ T ADCC CD16 cross-linking Chronic HIV infection iNKT MMP inhibitor AbbreviationsADCCantibody-dependent cellular cytotoxicity

NKnatural killer

HIV-1human immunodeficiency virus type-1

HCVhepatitis C virus

MMPmatrix metalloprotease

AIDSacquired immune deficiency syndrome

iNKTinvariant NKT

TCRT cell receptor


MHCmajor histocompatibility complex

PBMCperipheral blood mononuclear cell


FPDsformer plasma donors

MSMmen who have sex with men

DNdouble negative subset

HESNHIV-exposed seronegative


NKRnature killer cell receptor

CAP-CTMCobas Ampliprep-CobasTaqman

HBsAghepatitis B surface antigen


DMSOdimethyl sulphoxide


Xueying Fan and Liyan Zhu contributed equally to this work

Electronic supplementary materialThe online version of this article doi:10.1186-s12977-016-0313-6 contains supplementary material, which is available to authorized users.

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Autor: Xueying Fan - Liyan Zhu - Hua Liang - Zhe Xie - Xiangbo Huang - Shuo Wang - Tao Shen


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