tMMUNOLOGY
TODAY immunosuppressicm
with convcnlicmnl
the cause of graft xceptance effective
immunosuppression.
do 50 they
will have
case of long--tern
5hard and colIcagues have pro~licicd a comdwnsive rwiew of the xguments th;rt they lave
p~,+~~sly
two-way
raised
question ;erved
of
favt~ur
of their
of tolrrancr.
paradigm’
fail to shed
hey
in
new
uphether
Ho~.~ever,
the chirnerisrr
time
ob-
performed
of the tolerant
to the lws
induced
by the es-
af mixed chimer&m via bone
tablishment marrow
induced
removd of
drugs,
leads
ta
in the
why,
graft acceptance
state, whereas tolerance
light on the central
a transplant
following
In order
to explain
by immunosuppressive
the 4lograit
iu
or the result of
tran5plantation
of the recipient,
vr not the allagraft
E0r th
life-
of whether
is removed.
the same. There is IID purpose
not
c~nce are
persists regardless
in restating
the evidence that the mechanisms are the same, beyond emphasizing our agreement with Wood and Sachs that c=ipient Andrew
the mathematician,
#hen
:aced skeptics
after
proving
:heorcml, he said in ckct solved
FermaYs
that tither
the pmbkeem c)r gone
i-tire
Wiles,
mad.
irorn an ossified dogma
last
jjudged.The
madnessof
with drug-free
equating
tolerance
provokes
bnth qghst provided
weaning
is not part
reservediy
with
we paint
qqually
stop
theme
frum,
and
Sachs’
un-
caution
use
will
apply
of the mixed chim-
this advjce
in all management
isa
bee
pp.
dominant of con-
protocols
biologic
GVHD
and
safety
rejecticn,
more the
restriction d the acceptable
be
strategy
is applied
tissue
pod
handicap
will
if this
to xenotransplantatian.
that failure to find
concluded
microchimerism
donor
grave
a particularly
on
progressive
after ~IX~C&U~ human or-
gan transplantation, or in Clir&illy relevant surrogate
animal
plete sear&.
models,
studies
was from mlrltiple
sampling
an incorn-
imp&s
In our clinical
in which
sites,
the yield
converse
chimerism
way
in which
system is distorted
human
recipients
ity complex mtitinely
by
problem
many
cytp;lblation,
hist~mpatibil-
of major
require
the two-
bone marrow
months of immuno-
of graft-versus-host
dis-
ease CGVHDI. Even with an I-1LA inmmpat-
ibility of only mitt& these
one allele, the patient is corn-
to years
of dmg
therapy
ta avuid
Suggestions
contrary
to
the
IWO-way
paradigm Lowe been attributed tu us by inaccurate cit.Nions {summarized in kf. 21, not limited to the reports of weaning complications used by Wood and SachF to suppurt kheir contentinn that the meclx-u-&n~ of mgan- and bone-marrow-induced
DECEMBER
from
individual
with
yields
tiler-
1996
with
nvoidnnw
of
chronic
has been absolute in our hands.
r+ction
The conceptual ‘parking models’ nisms
complications.
to
paradigm.
depends
was
of using
flaw
to study tolerance
clRssica1 mecha-
in this issue (pp. 577-5841. We have left open the possibility that the organ parenchymal cells Facilitate vorable regional +agc
discussed
chime&m
previously
by contributing
microenvironmtnt, secretion
of
&ony-srimulating
G-CSF, other growth
transpIantatian
tributions
transplantation
Consequently,
of Wood, Sachs and many comprehend how the disorien-
that is
tirical
matching.
has been on the past and ccmtin-
about
nullification mechanism of dual cell populations. With each further increment in cytoreduction, successful
to a fa-
most likely by
granulocytt-macrofactor GM-CSF), and anti-growth
fac-
Chimer&P stood
Cretiewed
research
cut-red, it is impmtant
~uuppr~~sio~ to avoid graft rejection and the
transplantation4
In the latter context
uing tation
lacakions was C0mpar;ible reported by others. However, when the results were polect frnm the different sites in individual patients, all 30 tested patients had mjcrachimerism. In rat experiments where tissues could be retrieved without limit, the association of
ventiunal bone marrow
paradigm
malccules
device,
the
I antigens or as yet
in Ref. 3). It would ??eunjust not to pint out how dependent the evolution of the two-way
others. TO
is proportionate
the
by
We have
immunosuppression,
that they describe
Already,
drug
aglreing
out that their advice to clinical
584487).
While
Wood
mode&
erism
the pre-
to guide
of, or derivative
the two-way paradigm. nof EO reckles+
to be
chimer&m
the penalty
of
the east
engraftrnent
.
to its severity
However,
he had
weakening
or of using
SCSIC~and level of chimer&n
in proportion
A m&al
such thoughts. A new idea must be understood
enhances
cytoreduction
and extent of doncrr leukocyte
tom, soluble MHC class unidentified
the (see
observations only
Lolerance
0c-
to read classical conlikrahare
d
mixed
Fig. 3, p. 580). The hiscan
tn the context
be fully of the
undertwo-way