Critical role of caspases in the regulation of apoptosis and proliferation of mucosal T cells.
OBJECTIVE
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.
Sturm
Andreas
A
Division of Gastroenterology, Department of Medicine, University Hospital of Cleveland, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4952, USA.
Mohr
Susanne
S
Fiocchi
Claudio
C
D017209:Apoptosis; D020169:Caspases / Q000502:physiology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology
D020169:Caspases