Ultrastructural analysis of human natural killer cell activation

D. Zarcone, E. F. Prasthofer, F. Malavasi, V. Pistoia, A. F. LoBuglio, C. E. Grossi

Research output: Contribution to journalArticlepeer-review


In this study we describe characteristic ultrastructural changes of CD3- large granular lymphocytes (LGL), ie, natural killer (NK) cells, following stimulation with recombinant (r) interleukin 2 (IL 2) or r-γ interferon (r-γ IFN) and after interaction with K562 target cells (TC) or Sepharose-bound anti-Fc γ receptor (FcR) monoclonal antibody (MoAb). When compared to resting cells the cytolytic activity of r-IL 2- and r-γ IFN-stimulated cells against K562 TC was enhanced. The r-IL 2-stimulated LGL were larger and consistently displayed the shape and cytoskeletal rearrangement characteristic of activated cells. The Golgi apparatus was expanded, and the number of electron-dense granules and vesicles was increased. The ultrastructural changes in r-γ IFN-stimulated LGL were markedly different from those observed following r-IL 2 activation. Cells did not exhibit changes in size, shape, cytoskeletal organization, or in the structure of the Golig apparatus. However, r-γ IFN-stimulated cells exhibited distincitve changes in the structure and content of electron-dense granules with deaggregation of the matrix and parallel tubular arrays (PTAs). Within organelles apparently derived from the electron-dense granules, vesicular and tubular structures were noted that may be the morphological equivalent of cytotoxic factors produced by cytolytic effector cells. These ultrastructural observations indicate that r-IL 2 and r-γ IFN enhance the lytic ability of NK cells by acting on distinct cell machineries. The cytolytic ability was decreased when LGL were pretreated with K562 TC or immobilized anti-FcR antibody. In both experimental conditions cells displayed ultrastructural features indicating activation as well as loss of cytoplasmic granules and other Golgi-derived organelles. Stimulation of r-γ IFN- or r-IL 2-activated LGL with K562 TC or Sepharose-bound anti-FcR antibody decreased their cytolytic ability, with cells depleted of granules at the ultrastructural level. Intracytoplasmic fusion of granules and a massive release of the granule content were found in r-IL 2-stimulated cells, reminiscent of the mechanism of basophil degranulation. These observations suggest that multiple activation signals involving distinct surface membrane molecules induce release of cytolytic factors by both resting and activated NK cells.

Original languageEnglish
Pages (from-to)1725-1736
Number of pages12
Issue number6
Publication statusPublished - 1987

ASJC Scopus subject areas

  • Hematology


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