Appearance of granule-associated molecules during activation of cytolytic T-lymphocyte precursors by defined stimuli.
Lysis of target cells by cytolytic T lymphocytes (CTL) is associated with the exocytosis of cytoplasmic granules. Purified granules from CTL cell lines contain a pore-forming protein (perforin), tree serine esterases, granzyme A (60,000 MW), granzyme B (29,000 MW), and granzyme C (27,000 MW). We have compared the kinetics of appearance of cytolytic activity with that of perforin and granzyme A activity during activation of lymphocytes from normal animals with leukoagglutinin (LA) and recombinant interleukin-2 (rIL-2). Unstimulated lymph node cells do not express any of these activities, which appear between Day 3 and Day 4 of stimulation and increase rapidly to reach a pronounced peak on Day 6. On Day 7 all the activities are considerably lower, even though the cells still proliferate exponentially. There is a good correlation between the kinetics of appearance of all of these activities. Using antisera against perforin and against granzyme C, one can detect positive cytoplasmic granules in a small fraction of cells on Day 3; by Day 5, 80-90% of the cells are stained. This proportion decreases again on Day 7.
Garcia-Sanz
J A
JA
Genetics Unit, Swiss Institute for Experimental Cancer Research, Epalinges.
Velotti
F
F
MacDonald
H R
HR
Masson
D
D
Tschopp
J
J
Nabholz
M
M
D000818:Animals; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D005089:Exocytosis; D005260:Female; D053804:Granzymes; D006461:Hemolysis; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008815:Mice, Inbred Strains; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012697:Serine Endopeptidases / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D053804:Granzymes; C509216:Gzmc protein, mouse; D012697:Serine Endopeptidases