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


RESULTS
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.


CONCLUSIONS
Our results suggested that CD56+ T cells could mediate ADCC responses and the responses were impaired in chronic HIV-1 infection.
['Fan|Xueying|X|', 'Zhu|Liyan|L|', 'Liang|Hua|H|', 'Xie|Zhe|Z|', 'Huang|Xiangbo|X|', 'Wang|Shuo|S|', 'Shen|Tao|T|']
D000328:Adult D000920:Antibody-Dependent Cell Cytotoxicity D019002:CD56 Antigen D002908:Chronic Disease D060085:Coinfection D004151:Dipeptides D018450:Disease Progression D058851:GPI-Linked Proteins D015658:HIV Infections D020276:HIV Long-Term Survivors D006526:Hepatitis C D018451:Homosexuality, Male D006801:Humans D008297:Male D061965:Matrix Metalloproteinase Inhibitors D055611:Natural Killer T-Cells D017452:Receptors, IgG D016176:T-Lymphocyte Subsets D013997:Time Factors
CD56+ T ADCC CD16 cross-linking Chronic HIV infection MMP inhibitor iNKT