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

• Published in: Retrovirology Vol. 13; no. 1; p. 76
• Main Authors: Fan, Xueying, Zhu, Liyan, Liang, Hua, Xie, Zhe, Huang, Xiangbo, Wang, Shuo, Shen, Tao
• Format: Journal Article
• Language: English
• Published: England BioMed Central 04.11.2016
• Subjects: Adult; Antibody-Dependent Cell Cytotoxicity; CD56 Antigen - immunology; Chronic Disease; Coinfection - virology; Dipeptides - therapeutic use; Disease Progression; GPI-Linked Proteins - metabolism; Hepatitis C - virology; HIV Infections - blood; HIV Infections - immunology; HIV Infections - physiopathology; HIV Infections - virology; HIV Long-Term Survivors; Homosexuality, Male; Humans; Male; Matrix Metalloproteinase Inhibitors - therapeutic use; Natural Killer T-Cells - immunology; Receptors, IgG - metabolism; T-Lymphocyte Subsets - immunology; Time Factors; CD16 cross-linking; MMP inhibitor; CD56+ T; Chronic HIV infection; ADCC; iNKT
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/s12977-016-0313-6

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