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Expression: Lamina Propria T Cells Use Different cis-Elements than Peripheral Blood T Cells to Regulate Transactivation of IFN- Expression1
*
Inflammatory Bowel Disease Research Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
Laboratory of Experimental Immunology, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, MD 21702; and
Seoul Surgical Clinic, Seoul, Korea
Activation of lamina propria (LP) T cells via the CD2 pathway
enhances IFN-
(IFN-) secretion with further enhancement after
CD28 coligation. The molecular mechanisms regulating IFN- expression
in LP T cells remain unknown. Previous studies in PBL and T cell lines
identified cis- and trans-regulatory
elements in TCR-mediated expression of IFN-. This study examines CD2
and PMA/ionophore-responsive IFN- promoter elements. Activation of
LPMC via CD2-induced IFN- secretion and a parallel up-regulation of
mRNA expression. CD28 coligation enhanced mRNA stability without
up-regulating transcription as measured by nuclear run-on. Transfection
of a -2.7-kb IFN- promoter-reporter construct into PBL and LP
mononuclear cells (LPMC) revealed significant promoter activity after
CD2 activation, with additional transactivation after CD2/CD28
costimulation in PBL, but not in LPMC. Functional analysis using
truncated promoter fragments identified distinct
cis-regulatory regions selectively transactivating
IFN- expression in PBL compared with LPMC. In PBL, CD2 activation
elements reside within the -108- to +64-bp region. However, in LPMC
the upstream region between -204 and -108 bp was essential.
Transfection of the proximal and distal AP-1-binding elements, as well
as TRE/AP-1 constructs, revealed functional activation of AP-1
subsequent to CD2 signaling, with activation critical in PBL but
diminished in LPMC. Electromobility shift analysis using
oligonucleotides encompassing the proximal, distal, and
BED/AP-1-binding regions failed to demonstrate selective
transactivation after CD2 signaling of LPMC. This report provides
evidence that activation of LPMC results in transactivation of multiple
promoter elements regulating IFN- expression distinct from those in
PBL.
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