Antibody-dependent CD56+ T cell responses are functionally impaired in long-term HIV-1 infection.

Xueying Fan,Liyan Zhu,Hua Liang,Tao Shen,Zhe Xie,Xiangbo Huang,Shuo Wang

doi:10.1186/s12977-016-0313-6

Abstract

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

Highlights

Antibody-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
We found that stimulation with Abopsonized P815 cells led to a tremendous decrease of CD16+ population in CD56+ T cells and NK cells, but not in CD56− T subset (Fig. 2c), which was in accordance with their capacities to mediate ADCC response
A similar trend of antibody-dependent lytic capacity was found in NK cells but not in CD56− T cells. These results indicated that ADCC responses could be mediated by CD56+ T cells though the intensity was generally lower than the response mediated by classic CD56+ NK cells

Summary

Introduction

Antibody-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. CD56+ T cells are characterized by some NK celllike properties, such as the large granular lymphocyte morphology and the capacity to destroy NK-sensitive target cells [15, 16]. Compared with CD56+ T cells, the CD1d-restricted invariant NKT (iNKT) cells, which are characterized by expression of a specific T cell receptor (TCR) (Vα24-Jα18-Vβ11 in humans), play an important regulatory role in the innate and adaptive immune responses. These iNKT cells share partially phenotypic and functional properties with NK and CD56+ T cells [17]. Little is known about the potentials of CD56+ T cells in mediating ADCC responses and the association between CD56+ T cell-mediated ADCC responses and HIV-1 disease progression

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