Journal
JOURNAL OF IMMUNOLOGY
Volume 175, Issue 7, Pages 4392-4399Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.175.7.4392
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- NCI NIH HHS [CA82596] Funding Source: Medline
- NIAID NIH HHS [P01 AI35296] Funding Source: Medline
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Naive CD8 T cells that respond in vivo to Ag and costimnlation 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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