Licensing delineates helper and effector NK cell subsets during viral infection

Area of Science:

• Immunology
• Cellular Biology
• Infectious Disease

Background:

• Natural killer (NK) cells are categorized into subsets based on their interaction with self-MHC-I molecules, a process known as licensing or education.
• These subsets possess diverse functional capabilities influencing immune responses.

Purpose of the Study:

• To investigate the distinct functions of licensed and unlicensed NK cell subsets in adaptive immune responses during viral infections.
• To explore the migratory patterns, effector functions, and immunoregulatory roles of these NK cell subsets.

Main Methods:

• Analysis of NK cell subsets in mouse models of influenza and murine cytomegalovirus infection.
• Assessment of dendritic cell activation and antigen-specific CD8+ T cell responses.
• Comparison of human NK cell subset phenotypes with findings in mice.

Main Results:

• Unlicensed NK cells migrated to lymph nodes, produced GM-CSF, promoted dendritic cell expansion, and enhanced T cell responses.
• Licensed NK cells preferentially migrated to infected tissues and produced IFN-γ.
• Human NK cell subsets displayed comparable phenotypic characteristics to those observed in mice.

Conclusions:

• A clear functional division exists between licensed and unlicensed NK cell subsets.
• Unlicensed NK cells are crucial for stimulating adaptive immunity by priming immune responses.
• Licensed NK cells function as effector cells during viral infections.