Response to Wood and Sachs

Response to Wood and Sachs

tMMUNOLOGY TODAY immunosuppressicm with convcnlicmnl the cause of graft xceptance effective immunosuppression. do 50 they will have case of lon...

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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