Signal 3 tolerant CD8 T cells degranulate in response to antigen but lack granzyme B to mediate cytolysis

Julie M. Curtsinger, Debra C. Lins, Christopher M. Johnson, Matthew F. Mescher

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

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."

Original languageEnglish (US)
Pages (from-to)4392-4399
Number of pages8
JournalJournal of Immunology
Volume175
Issue number7
DOIs
StatePublished - Oct 1 2005

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