Ultrastructural characteristics of human T cell clones with various cytolytic activities

Fifteen T cell clones with different (specific, antibody-dependent or natural killer-like) cytolytic activity were derived from mixed lymphocyte culture activated T cells and analyzed for their morphological characteristics and, in some instances, for their surface markers. All of the five cytolytic clones analyzed by electron microscopy possessed numerous electron-dense granules and in some instances multivesicular bodies, with or without an electron-dense matrix, that are the putative precursors of the granules. In addition, light microscopy examination of semithin sections of other ten cytolytic clones showed that the large majority of the cells in each clone had numerous toluidine blue-stained cytoplasmic granules. It is of note that nine clones without detectable cytolytic activity analyzed by electron microscopy did not possess granules and presented the features of large agranular blasts. Ten cytolytic clones were analyzed for different surface markers including rosette formation with sheep erythrocytes (E rosettes), receptors for the Fc portion of IgG or IgM (FcγR and FcμR) and a group of antigens recognized by monoclonal antibodies including Ia, 4F2, OKT8 or OKT4. All the clones were E-rosette⁺, Ia⁺ and 4F2⁺. Expression of FcγR was restricted to the clones active in antibody-dependent cell-mediated cytotoxicity. Expression of OKT8 and OKT4 antigens was variable; in particular, five clones were OKT8⁺/OKT4^-, whereas the other five expressed the OKT8^-/OKT4⁺ phenotype. It is noteworthy that the ultrastructural features of cytolytic T cell clones are similar to those of large granular lymphocytes, known to be the only lymphoid cells in normal peripheral blood which possess cytolytic activity. Thus, it is possible that the presence of electron-dense granules may represent a morphological marker for all human cytolytic lymphocytes.