 |
リウマチ Vol.43 No.2 indexに戻る
 |
リウマチ Vol.43 No.2 |
 |
|
|
 |
|
|
Involvement of a Negative Coreceptor
PD-1 in Autoimmunity and Tumor Surveillance P.170
|
|
| |
| Tasuku HONJO |
| Dept. of Medical Chemistry and Molecular Biology,
Graduate School of Medicine, Kyoto University |
| |
| 特別講演 |
PD-1 is a receptor of the Ig superfamily that
negatively regulates T cell antigen receptor signaling by interacting
with the specific
ligands（PD-L）and is suggested to play a role in the maintenance of
self-tolerance. Disruption of the gene for PD-1 in BALB/c but not
in BALB/c RAG-2-/- mice caused dilated cardiomyopathy with
severely impaired contraction and sudden death by congestive heart
failure. Affected hearts showed diffuse deposition of IgG on the
surface of cardiomyocytes. All of the affected PD-1-/-mice
exhibited high-titered circulating IgG autoantibodies reactive to
a 33kDa protein expressed specifically on the surface of cardiomyocytes.
These results indicate that PD-1 may be an important factor contributing
to the prevention of autoimmune diseases.
We also examined possible roles of the PD-1/PD-L system in tumor
immunity. Transgenic expression of PD-L1 in P815 tumor cells rendered
them less susceptible to the specific T cell antigen receptor-mediated
lysis by cytotoxic T cells in vitro, and markedly enhanced their
tumorigenesis and invasiveness in vivo in the syngeneic hosts. Growth
of the myeloma cells in normal syngeneic mice was inhibited significantly
by the administration of anti-PD-L1 Ab in vivo. These results suggest
that the expression of PD-L1 can serve as a potent mechanism for
potentially immunogenic tumors to escape from host immune responses
and that blockade of interaction between PD-1 and PD-L may provide
a promising strategy for specific tumor immunotherapy. |
|
 |
|
|
