Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes
The Journal of Experimental Medicine,
Год журнала:
2025,
Номер
222(4)
Опубликована: Янв. 17, 2025
Tuberculosis
(TB)
is
a
major
health
burden
worldwide
despite
widespread
intradermal
(ID)
BCG
vaccination
in
newborns.
We
previously
demonstrated
that
changing
the
route
and
dose
from
5
×
105
CFUs
ID
to
107
i.v.
resulted
prevention
of
Mycobacterium
tuberculosis
(Mtb)
infection
TB
disease
highly
susceptible
nonhuman
primates.
Identifying
immune
mechanisms
protection
following
will
facilitate
development
more
effective
vaccines
against
TB.
Here,
we
depleted
lymphocyte
subsets
prior
during
Mtb
challenge
BCG-vaccinated
macaques
identify
those
necessary
for
protection.
Depletion
adaptive
CD4
T
cells,
but
not
CD8αβ
loss
with
increased
burdens
dissemination,
indicating
cells
are
critical
BCG-mediated
unconventional
CD8α-expressing
lymphocytes
(NK
innate
CD4+CD8α+
double-positive
cells)
abrogated
most
BCG-immunized
macaques,
supporting
further
investigation
into
which
these
cell
contribute
after
vaccination.
Язык: Английский
CD4 T cells and CD8α+ lymphocytes are necessary for intravenous BCG-induced protection against tuberculosis in macaques
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 17, 2024
Tuberculosis
(TB)
is
a
major
cause
of
morbidity
and
mortality
worldwide
despite
widespread
intradermal
(ID)
BCG
vaccination
in
newborns.
We
previously
demonstrated
that
changing
the
route
dose
from
5×105
CFU
ID
to
5×107
intravenous
(IV)
resulted
prevention
infection
disease
rigorous,
highly
susceptible
non-human
primate
model
TB.
Identifying
immune
mechanisms
protection
for
IV
will
facilitate
development
more
effective
vaccines
against
Here,
we
depleted
select
lymphocyte
subsets
vaccinated
macaques
prior
Mtb
challenge
determine
cell
types
necessary
protection.
Depletion
CD4
T
cells
or
all
CD8α
expressing
lymphoycytes
(both
innate
adaptive)
loss
most
macaques,
concomitant
with
increased
bacterial
burdens
(~4-5
log10
thoracic
CFU)
dissemination
infection.
In
contrast,
depletion
only
adaptive
CD8αβ+
did
not
significantly
reduce
disease.
Our
results
demonstrate
CD8α+
lymphocytes
are
critical
BCG-induced
protection,
supporting
investigation
how
eliciting
these
their
functions
can
improve
future
TB
vaccines.
Язык: Английский
Advances in Subclinical and Clinical Trials and Immunosuppressive Therapies in Xenotransplantation
Xenotransplantation,
Год журнала:
2025,
Номер
32(3)
Опубликована: Май 1, 2025
ABSTRACT
Organ
transplantation
remains
the
foremost
effective
intervention
for
end‐stage
organ
failure.
Nevertheless,
scarcity
of
donors
has
resulted
in
prolonged
waiting
times
countless
patients
globally.
The
advent
xenografts
presents
a
promising
solution
to
shortage
crisis.
Although
utilization
long
history,
it
is
only
recent
years
that
breakthroughs
genetically
modified
pigs
have
rendered
successful
xenotransplantation
feasible
option.
In
past
4
years,
numerous
subclinical
and
clinical
trials
involved
from
humans.
However,
outcomes
been
disappointing,
necessitating
reassessment
basic
preclinical
research
address
emerging
challenges.
Furthermore,
immunosuppressive
therapies
remain
essential
xenotransplantation.
range
agents,
encompassing
traditional
immunosuppressants
monoclonal
antibodies
such
as
anti‐CD154/CD40
antibodies,
exhibits
considerable
diversity.
most
drug
combination
achieving
optimal
efficacy
elusive.
This
review
will
offer
succinct
overview
results
trials.
Moreover,
highlight
advancements
strategies
discuss
potential
future
directions
this
field.
Язык: Английский