MHC-RESTRICTED, ANTIGEN SPECIFIC, GRANULE EXOCYTOSIS FROM HELPER T CELLS: ANOTHER INDICATOR OF RECEPTOR MEDIATED T CELL ACTIVATION

Abstract

Recently, it has been observed that some T cells contain trypsin-like serine esterases. Helper T cell clones derived in our laboratory contain hight levels of these enzymes derived in our laboratory contain high levels of these enzymes (BLT esterase), which are associated with cytoplasmic granules. Using supernatant release of these enzymes as marker, we examined granule exocutosis as consequence of T cell activation via the T cell receptor. Clones 8-5 (Ab, KLH), 10-2(Ab, KLH) and A13 (Ak, KLH) all released enzymatic activity over background (consititutive release) when cultured with antigen plus syngeneic antigen presenting cells (APC) 37%, 50%, 27% of total activity, respectively). APC alone contained negligible enzyme acitivity. Incubation of clones with syngenic APC or with antigen plus non-syngeneic APC gave only background release. Other stimuli with induced strong granule exocytosis were conconavalin A and an antibody against the mouse T3 complex. Using antigen pulsed APC, exocytosis was detected as early as one hour after the initiation of T cell stimulation. In contrast, when activation was induced by incubation of cloned T cells with interleukin 2 (IL-2), no secretion above background was observed despite the fact that substantial DNA synthesis occurred. Thus, it appears that granule exocytosis may be another means of analyzing T cell activation pathways initiated by T cell receptor-ligand interactions. Furthermore, these activation sequences may be distinquished from those occurring after IL-2 interaction with its receptor, since the latter event does not induce granule exocytosis.