TY - JOUR
T1 - Signal 3 tolerant CD8 T cells degranulate in response to antigen but lack granzyme B to mediate cytolysis
AU - Curtsinger, Julie M.
AU - Lins, Debra C.
AU - Johnson, Christopher M.
AU - Mescher, Matthew F.
PY - 2005/10/1
Y1 - 2005/10/1
N2 - Naive CD8 T cells that respond in vivo to Ag and costimulation in the absence of a third signal, such as IL-12, fail to develop cytolytic function and become tolerized. We show in this study that CD8 T cells purified from TCR transgenic mice and stimulated in vitro in the presence or absence of IL-12 form conjugates with specific target cells, increase intracellular Ca2+, and undergo degranulation to comparable extents. Perforin is also expressed at comparable levels in the absence or presence of a third signal, but expression of granzyme B depends upon IL-12. Levels of granzyme B also correlate strongly with the cytolytic activity of cells responding in vivo. In contrast, an increase in CD107a (lysosomal-associated membrane protein 1) expression resulting from degranulation cannot distinguish in vivo generated lytic effector cells from tolerized, noncytolytic cells. Thus, it appears that cells rendered tolerant as a result of stimulation in the absence of a third signal fail to lyse target cells because they are "shooting blanks."
AB - Naive CD8 T cells that respond in vivo to Ag and costimulation in the absence of a third signal, such as IL-12, fail to develop cytolytic function and become tolerized. We show in this study that CD8 T cells purified from TCR transgenic mice and stimulated in vitro in the presence or absence of IL-12 form conjugates with specific target cells, increase intracellular Ca2+, and undergo degranulation to comparable extents. Perforin is also expressed at comparable levels in the absence or presence of a third signal, but expression of granzyme B depends upon IL-12. Levels of granzyme B also correlate strongly with the cytolytic activity of cells responding in vivo. In contrast, an increase in CD107a (lysosomal-associated membrane protein 1) expression resulting from degranulation cannot distinguish in vivo generated lytic effector cells from tolerized, noncytolytic cells. Thus, it appears that cells rendered tolerant as a result of stimulation in the absence of a third signal fail to lyse target cells because they are "shooting blanks."
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U2 - 10.4049/jimmunol.175.7.4392
DO - 10.4049/jimmunol.175.7.4392
M3 - Article
C2 - 16177080
AN - SCOPUS:25444468825
SN - 0022-1767
VL - 175
SP - 4392
EP - 4399
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -