Activation of primary T lymphocytes results in lysosome development and polarized granule exocytosis in CD4+ and CD8+ subsets, whereas expression of lytic molecules confers cytotoxicity to CD8+ T cells

Lytic granule exocytosis is the major cytotoxic mechanism used by CD8 cytotoxic lym- phocytes. CD8 T cells acquire this effector func- tion in the process characterized by lysosomal bio- genesis, induction of expression of cytolytic mole- cules, and their selective sorting into the lysosomal vesicles. However, temporal relation of these dif- ferentiation stages during T cell activation has not been defined precisely. Also, although CD4 T cells typically do not express lytic molecules as a consequence of activation, and therefore, do not acquire granule exocytosis-mediated lytic func- tion, it is not clear whether CD4 T cells are able to degranulate. By using in vitro TCR stimulation of primary mouse lymphocytes, we found that poly- clonally activated CD4 T cells degranulate upon TCR ligation and polarize enlarged lysosomal gran- ules in response to target cell recognition, despite the lack of granule exocytosis-mediated cytotoxic- ity. Upon TCR stimulation, resting CD8 T cells rapidly express lytic molecules and acquire potent lytic function early in activation. Maximal cytolytic potential, however, depends on enlargement of ly- sosomal granules during the subsequent activation stages. Thus, polyclonal TCR stimulation of resting T cells results in development of lysosomal gran- ules and their release upon TCR engagement in CD4 and CD8 T cells, but only CD8 T cells acquire lytic function as a result of induction of expression of lytic molecules. J. Leukoc. Biol. 80: 827-837; 2006.