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In the CARGO study
(Deng, 2006), several genes were found to be related to acute
cellular cardiac allograft rejection, but interestingly, in this
genomic era, very little is known about many of them. Furthermore,
most of them has never been implicated in the acute cellular
rejection process. We are currently focusing on the study of some of
those genes and try to understand which is the real connection
between the molecular classifier that has been developed by the
CARGO investigators (AllomapTM Molecular Test) and the
rejection process.
The Inhibitory Receptor G6b-B
in Peripheral CD4+ Lymphocytes
The human G6b-B gene,
located in the class III region of MHC, encodes a cell surface receptor of the Ig
superfamily. This receptor potentially interacts with SHP-1/SHP-2 by
the ITIMs in its cytoplasmic domain, triggering inhibitory signaling
pathways. Our previous studies, have identified that the expression
of the G6b-B gene in peripheral blood monocytes (PBMC) is impaired during acute
cell-mediated allograft rejection. To further understand a
biological role of this molecule, we investigated its expression in
the different populations of human PBMC using RT-PCR analysis. G6b-B is predominantly expressed in CD4+ T cells
as compared with
CD8+ T cells (>3.1 fold), B cells (>3.5 fold) and monocytes (>2.1
folds). On a 1.9 kb upstream sequence of the translation
start site of the gene, we found a putative cis-acting element for the transcriptional
factor STAT6 and SMAD3/4. The response of the gene
expression to the human cytokines IL-4, TNF-a, IL-10 or
IL-2, showed that G6b-B mRNA level is significantly increased by
IL-4, but not altered by other cytokines.
Based on our current
results, the G6b-B gene expression would be
restricted to peripheral CD4+ T cells, and potentially regulated by
Th2 cells to mediate an inhibitory role in inflammatory reaction. |
