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.
Department of Microbiology and Center of Infectious Diseases, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
Xueying
X
Fan
Department of Microbiology and Center of Infectious Diseases, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
Liyan
L
Zhu
State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China CDC, Beijing, China.
Hua
H
Liang
Department of Microbiology and Center of Infectious Diseases, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
Zhe
Z
Xie
Department of Microbiology and Center of Infectious Diseases, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
Xiangbo
X
Huang
State Key Laboratory of Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, China CDC, Beijing, China.
Shuo
S
Wang
Department of Microbiology and Center of Infectious Diseases, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China. taoshen@hsc.pku.edu.cn.
Tao
T
Shen
D000328:Adult; D000920:Antibody-Dependent Cell Cytotoxicity; D019002:CD56 Antigen / Q000276:immunology*; D002908:Chronic Disease; D060085:Coinfection / Q000821:virology; D004151:Dipeptides / Q000627:therapeutic use; D018450:Disease Progression; D058851:GPI-Linked Proteins / Q000378:metabolism; D015658:HIV Infections / Q000097:blood / Q000276:immunology* / Q000503:physiopathology* / Q000821:virology; D020276:HIV Long-Term Survivors; D006526:Hepatitis C / Q000821:virology; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use; D055611:Natural Killer T-Cells / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors
D019002:CD56 Antigen; D004151:Dipeptides; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D061965:Matrix Metalloproteinase Inhibitors; C078131:N-(2(R)-2-(hydroxamidocarbonylmethyl)-4-methylpentanoyl)-L-tryptophan methylamide; C522918:NCAM1 protein, human; D017452:Receptors, IgG
ADCC; CD16 cross-linking; CD56+ T; Chronic HIV infection; MMP inhibitor; iNKT