Abstract:
BACKGROUND & AIMS:Caspases are critical mediators of apoptosis and proliferation of peripheral blood T cells (PBT), but their role in lamina propria T cells (LPT), a cell population highly susceptible to apoptosis, has not been explored. METHODS:RA(+), RO(+) PBT, and LPT were activated with CD3, CD2, and CD28 antibodies, and caspase activity, apoptosis, and proliferation were measured by a fluorometric assay, DNA content, and thymidine incorporation, respectively. Levels of FLIP, an endogenous inhibitor of caspase 8, were measured by immunoblotting. RESULTS:In RA(+) and RO(+) PBT, activation leads to significant increase of caspase activity but not cell death, whereas in LPT a lower elevation of caspase activity was followed by a marked degree of apoptosis. Based on the results of its inhibition, caspase 8 seemed to be essential for LPT apoptosis but, in contrast to RA(+) PBT, had no effect on proliferation. In addition, compatible with their differential susceptibility to apoptosis, levels of FLIP were lower in LPT than PBT. CONCLUSIONS:The high susceptibility of LPT to apoptosis is associated with a distinct regulation of caspase 8 activity, which seems to reflect their mucosal origin rather than simply their memory status. This unique behavior may allow proper control of mucosal T-cell proliferation while still permitting elimination by apoptosis in the face of excessive antigenic pressure.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Sturm A,Mohr S,Fiocchi Cdoi
10.1053/gast.2002.32996keywords:
subject
Has Abstractpub_date
2002-05-01 00:00:00pages
1334-45issue
5eissn
0016-5085issn
1528-0012pii
S0016508502367672journal_volume
122pub_type
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