Human CD3+CD56+NKT-like cells express a range of complement receptors and C3 activation has negative effects on these cell activity and effector function

• Published in: Human immunology 2021-09, Vol.82 (9), p.625-633
• Main Authors: Min, Xiao-Yun, Liu, Cheng-Fei, Cao, Bo, Zhang, Ting, Yang, Xiao, Ma, Ning, Wang, Na, Li, Ke
• Format: Article
• Language: English
• Subjects: Biomarkers; CD3 Complex - metabolism; CD3+CD56+NKT; CD56 Antigen - metabolism; Cells, Cultured; Complement Activation - immunology; Complement C3 - immunology; Complement receptors; Cytotoxicity, Immunologic; Gene Expression; Humans; Immunophenotyping; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Natural Killer T-Cells - immunology; Natural Killer T-Cells - metabolism; Receptors, Complement - genetics; Receptors, Complement - metabolism; Regulation
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/j.humimm.2021.06.001

CD3+CD56+NKT-like cells are a rare population of lymphocytes that serve important roles in various types of immune-related diseases, and particularly in cancer. The complement system regulates inflammatory and immune responses by interacting with complement receptors expressed on a range of immune cells. However, whether CD3+CD56+NKT-like cells are regulated by the complement system has still not been definitively determined. In the present study, the expression of complement receptors and regulators in gated CD3+CD56+NKT-like cells isolated from human peripheral blood was assessed using PCR and flow cytometry. The results showed that human CD3+CD56+NKT-like cells expressed a range of complement receptors and regulators, such as CR3, C3aR, C5aR, C5L2, CD46 and CD55. Furthermore, the presence of complement component 3 (C3), a key component in complement activation in culture supernatant, mitigated the activity, IFN-γ production and killing function of CD3+CD56+NKT-like cells. The present study provides evidences supporting the relationship between complement activation and functional modulation of CD3+CD56+NKT-like cells, expanding our knowledge of the complement regulatory network, and also highlighting a potential target for treatment of numerous immune-related diseases, particularly NKT cell-based tumor adoptive immunotherapy.