Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Anti-CD3ε mAb improves thymic architecture and prevents autoimmune manifestations in a mouse model of Omenn syndrome: therapeutic implications.
[omenn syndrome]
Omenn
syndrome
(
OS
)
is
an
atypical
primary
immunodeficiency
characterized
by
severe
autoimmunity
because
of
activated
T
cells
infiltrating
target
organs
.
The
impaired
recombinase
activity
in
OS
severely
affects
expression
of
the
pre-
T
-
cell
receptor
complex
in
immature
thymocytes
,
which
is
crucial
for
an
efficient
development
of
the
thymic
epithelial
component
.
Anti-
CD
3
ε
monoclonal
antibody
(
mAb
)
treatment
in
RAG
2
(
-
/
-
)
mice
was
previously
shown
to
mimic
pre-
TCR
signaling
promoting
thymic
expansion
.
Here
we
show
the
effect
of
anti-
CD
3
ε
mAb
administration
in
the
RAG
2
(
R
229
Q
)
mouse
model
,
which
closely
recapitulates
human
OS
.
These
animals
,
in
spite
of
the
inability
to
induce
the
autoimmune
regulator
,
displayed
a
significant
amelioration
in
thymic
epithelial
compartment
and
an
important
reduction
of
peripheral
T
-
cell
activation
and
tissue
infiltration
.
Furthermore
,
by
injecting
a
high
number
of
RAG
2
(
R
229
Q
)
progenitors
into
RAG
2
(
-
/
-
)
animals
previously
conditioned
with
anti-
CD
3
ε
mAb
,
we
detected
autoimmune
regulator
expression
together
with
the
absence
of
peripheral
immunopathology
.
These
observations
indicate
that
improving
epithelial
thymic
function
might
ameliorate
the
detrimental
behavior
of
the
cell-autonomous
RAG
defect
.
Our
data
provide
important
therapeutic
proof
of
concept
for
future
clinical
applications
of
anti-
CD
3
ε
mAb
treatment
in
severe
combined
immunodeficiency
forms
characterized
by
poor
thymus
function
and
autoimmunity
.