期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 46, 期 7, 页码 1644-1655出版社
WILEY
DOI: 10.1002/eji.201546232
关键词
CD28 costimulation; CD8(+) T cells; CD8(+) effector cell; CD8(+) T-cell memory
类别
资金
- Deutsche Forschungsgemeinschaft [IRTG 1522]
- Frauenburo of the University of Wurzburg
The role of CD28-mediated costimulation in secondary CD8(+) T-cell responses remains controversial. Here, we have used two tools - blocking mouse anti-mouse CD28-specific antibodies and inducible CD28-deleting mice - to obtain definitive answers in mice infected with ovalbumin-secreting Listeria monocytogenes. We report that both blockade and global deletion of CD28 reveal its requirement for full clonal expansion and effector functions such as degranulation and IFN-gamma production during the secondary immune response. In contrast, cell-intrinsic deletion of CD28 in transferred TCR-transgenic CD8(+) T cells before primary infection leads to impaired clonal expansion but an increase in cells able to express effector functions in both primary and secondary responses. We suggest that the proliferation-impaired CD8(+) T cells respond to CD28-dependent help from their environment by enhanced functional differentiation. Finally, we report that cell-intrinsic deletion of CD28 after the peak of the primary response does not affect the establishment, maintenance, or recall of long-term memory. Thus, if given sufficient time, the progeny of primed CD8(+) T cells adapt to the absence of this costimulator.
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