Ultrastructural analysis of human natural killer cell activation

Area of Science:

• Immunology
• Cell Biology
• Cytotoxicity

Background:

• Large granular lymphocytes (LGLs), including natural killer (NK) cells, are crucial for innate immunity.
• Understanding NK cell activation and degranulation mechanisms is vital for immunotherapy development.

Purpose of the Study:

• To investigate the ultrastructural changes in NK cells stimulated by recombinant interleukin 2 (r-IL 2) or recombinant gamma interferon (r-gamma IFN).
• To examine NK cell ultrastructure after interaction with K562 target cells or anti-Fc gamma receptor (FcR) antibody.
• To correlate ultrastructural changes with NK cell cytolytic activity.

Main Methods:

• Transmission electron microscopy was used to observe ultrastructural changes in NK cells.
• NK cells were stimulated with r-IL 2, r-gamma IFN, K562 target cells, or Sepharose-bound anti-FcR monoclonal antibody.
• Cytolytic activity assays were performed to measure NK cell function.

Main Results:

• r-IL 2 and r-gamma IFN enhanced NK cell cytotoxicity via distinct ultrastructural pathways.
• r-IL 2 induced NK cell enlargement, cytoskeletal rearrangement, and Golgi expansion.
• r-gamma IFN altered granule structure and content, suggesting cytotoxic factor release.
• NK cell interaction with target cells or anti-FcR antibody decreased cytotoxicity, accompanied by granule depletion and release.

Conclusions:

• r-IL 2 and r-gamma IFN activate distinct cellular machineries to enhance NK cell lytic ability.
• NK cell degranulation and release of cytotoxic factors can be triggered by multiple activation signals.
• These findings provide morphological insights into NK cell activation and effector function.