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Gastroenterology. 2002 May;122(5):1334-45.

Critical role of caspases in the regulation of apoptosis and proliferation of mucosal T cells.

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1
Division of Gastroenterology, Department of Medicine, University Hospital of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4952, USA.

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.

PMID:
11984520
[Indexed for MEDLINE]
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