From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
Antigenic
Behavior
By ERIc
S
of the
R. BROWN,
Invircc
S-63
Mouse
GREENSPAN
TUDIES
ANTIBODIES This
in micerepresents
injected
have
been OF reported.1
study
1 ) and a study
of the correlation
between
tests
The
(table
obtained
cell
from
passage
vivors
jected
originally
was
mice
in which
our
laboratories
in
Comparative
for
to
tolerant
extracts
Because
SCHWARTZ
5-63
anwithextension
in vitro
and
this
leukemia
virus
of that
work
in vivo protec-
had
form,
immunologic
lation
of the
virus
had
years.
the
cells
that
by
from
have
protection
in rabbits.
newborn
tissues
ascites
maintained
obtained
miCe
between
mouse
of
been
Serum
newborn
produced
antibodies,
normal
extraction
sur-
been
in-
afforded
by
In some
experiments,
rabbits
were
first made
and
were
later
challenged
tissues.
virus
latent
DNA
leukemia
several
performed
to
of leukemic
of
protects
and
antisera
mouse
tissue
immunologically
with
were
by
form
mice
studies
sera
avoid
isolated
this
of S-63 virus-injected
with this agent.
convalescent
in order
Virus
2).
virus
S-63
0.
AND STEVEN
( table
tion
Leukemia
apparently
been
studies
to the
carrier
were
carried
also
in
the
undertaken
ascites
to
cells
determine
in
a
the
re-
cell.
METHODS
Preparation
S-63
of Antigens
Virus
viously
were
Young
with
adult
ICR
mice,
the
virus,
were
killed
4
weeks
after
inoculation
( 2 to
apparent
nomegaly,
Cu.
Antigen:
injected
hepatomegaly,
thymic
at
enlargement
approximately
a
time
) . At
and
a
20
when
gross
that
time
Gm.
weight,
the
leukocytosis
of
pre-
leukemia
animals
had
sple-
50,000
averaging
WBC/
mm.
Twenty
per
cent
with
tissues
cent
homogenates
scissors
in
hyaluromdase
at
temperature,
ground
of
Hank’s
a
in
pH
a
their
leukemic
balanced
of
Ten
7.2.
Broek
salt
The
tissues
homogenate
glass
were
( HBSS
solution
was
homogenizer,
prepared
digested
and
From the Hematology
Cook County
Hospital
Supported
by a grant
and No. CRTY
5092.
Department
of The Hektoen
and Northwestern
University
from the McCormick
Fund
the
First
Eiuc
Institute
submitted
R.
Jan.
BROWN,
for
Medical
vestigator,
Department
Chicago,
Illinois.
SrEvi
versity
Medical
School,
Medical
Research,
14, 1965;
accepted
for publication
Senior
0.
SCHWARTZ,
NI.D.:
and Director,
Department
Chicago,
Illinois.
mincing
for
1.5
1
centrifuged
hour
for
the
at
20
porcelain
an 0.45
Model
L
per
mg.
room
minutes
filter,
then
Millipore
centrifuge.
Irtitute
for Medical
Research
of
Medical
School,
Chicago,
Illinois.
and USPHS
Grants
No. CA 03321
Investigator,
Department
Research,
Chicago,
Illinois.
IRVING
of Hematology,
The Hektoen
PH.D.:
by
) containing
at 900
g. The supernatant
fluid was clarified
through
a Selas CFF
diluted
1 to 5 with
HBSS.
The
clarified
solution
was
passed
through
filter and was then centrifuged
at 100,000
g for
1 hour
in a Spinco
for
in
symptoms
May
18,
of
1965.
Hematology,
The Hektoen
M.D.:
Senior
inInstitute
for
Medical
Research,
Professor
of Medicine,
Northwestern
Uniof Hematology
of
The Hektoen
Institute
GREENSPAN,
65
BLOOD,
VOL.
27,
No.
1
(JANUARY),
1966
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
66
BROWN,
The
resulting
of
pellet
original
animal
ml.
a
pended
The
were
in
and
were
by
was
Garb
in
his
fresh
against
is,
used
for
Production
of
ml.
1.0
was
ml.
both
mg.
to
incomplete
and
female
were
of
leukemic
antigens
for
the
linmunodiffusion:
as
as
#{176}Thirty-eight
were
duced
in
ascites
virus
producing
the
animals
intra-
250,000
the
dose
4 consecutive
the
rabbits
days
were
tested
immunodiffusion,
test.
Immune-tolerant
mouse
tissue
antigen
antigens-
or ascites
i,nmune-tolerant
in
cells.
intravenously.
One
repeated
bled
later
week
the
the
later.
serum
cell
2.0 ml.
and
adjuvant
a
and
were
first injections
week
incomplete
was
rabbits
) . The
HBSS
immune-tolerant
the
pellet
ml.
Fourteen
to
tested
for
was
of
given
the
rabbits
first
dose
of
were
antigen
intramuscularly
material,
treated
and
mixed
in
consisted
with
0.5
an
ml.
a
2.0
of
given
equal
volume
intramuscularly.
Rabbits
in
age
to
the
antibodies.
in
the
were
given
comparable
for
method
increasing
for
virus
Freund’s
Here
2.0
were
the
injected
cells.
cells.
later
and
weeks
mm.
ml.
of
antigen,
in Normal
Test:
used
these
The
advantages
the
microprecipitin
and
The
immune-tolerant
Those
rabbits
rabbits
immune-tolerant
rabbits
of
at
received
the
the
time
same
dose
experiments.
was
used
as
a screening
this
test,
have
been
immunodiffusion
test has
Agar
(Difco),
7/10
newborn
for
test
disadvantages
Noble
described.4
Four
resus-
Antibodies
Microprecipitin
previously
ascites
adjuvant,
used
0.5
This
resuspended
rabbits
challenge
well
and
Rabbits
animals
viral
ml.
14
of
microprecipitin,
S-63
cells/cu.
and
the
2 weeks
of Antibodies
of
as
HBSS,
approximately
normal
tissues,
vilume
the
given
of
of Freund’s
Testing
gently
in
line
HBSS
were
anaphylaxis
the
leukemic
equal
and
to
N/mb.)
One
Normal
were
times
modification
contain
against
either
intramuscularly.
normal
those
intravenously.
Production
an
of
by
react
( 1,500,000
challenge,
immunity
similar
to
cells
with
last
end
in Immune-Tolerant
given
the
produce
(0.5
in
continued
cutaneous
with
intramuscularly
were
after
the
to
a
0.1
was
antigens
failed
challenge
ascites
mixed
mixture
manner
un-
suspensions
cell-transmitted
times
rabbits
with
dose
At
passive
sera
immunity
of
against
To
of
specific
suspensions
activity
3
to
starting
This
tissue
modified
whose
of Antibodies
days
3
established
albino
adjusted
given
mouse
a
those
purposes
produce
suspension
21
cent
tissues
washed
rabbits#{176} by
antigen
were
nonnal
and
animals-that
of the
mice
untreated,
per
the
then
washed
Newborn
tissue
injections
iminunofluorescence,
consisted
For
newborn
Rabbits
newborn
ll,23
normal
Daily
antibodies
given
from
Twenty
an
were
in Newborn
induced
and
with
mm.
To
diluent/Gm.
antigen.
to
mincing,
were
from
They
by 0.1 cc. daily until 1.0 ml. was reached.
and thereafter
once weekly
for 10 weeks.
were
after
obtained
laboratory.
Tolerance
tolerance
peritoneally
for
of
viral
prepared
nodes.
cells
1 ml.
the
mice.
were
lymph
The
of
as
intraperitoneally
ICR
adult
prepared,
grinder.
cells
our
of Immune
Immune
cells/cu.
given
antigens
and
basis
used
SCHWARTZ
use.
Induction
reported
Gm.
tissue
the
was
) was
livers
Tissue
ascites
carried
for
20
on
pellet
AND
counted.
Cells:
leukemia
young
HBSS
HBSS
N/mb.
spleens,
Broek
and
Ascites
mg.
Normal
using
in
Ten
resuspended,
of
mice
tissues
in
to
in
resuspended
(0.5
Antigen:
ICR
inoculated
these
ml.
0.1
Tissue
again
This
intravenously
Normal
ground
suspended
weight.
inoculations,
and 0.2
of
was
tissue
GREENSPAN
were
rabbits
antiascites
were
cell
individually
and
originally
three
tested
been
per
injected.
for
for
S-63
immune
since
in
survived
injection.
tolerance
then
it
was
physiologic
to
The
and
technic,
discussed.4
suspended
Seven
virus
The
modified
slightly
cent,
test.
previously
maturity.
antisera
pooled.
pro-
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
THE
S-63
saline
MOUSE
LEUKEMIA
solution,
solving
containing
the
were
agar,
coated
poured
into
for cutting
recharged
the agar.
Passive
was
with
a
dish.
the
at
0.005
Merthiolate
each
of
cent
added
glycerin
A 5-hole
All plates
3 times
Cutaneous
per
was
mixture
wells.
least
67
VIRUS
cadmium
acetate,
to a final
dilution
and
were
( every
Anaphylactic
Feinberg
held
third
a
minimum
(PCA):
The
25
10
of
(Colab)
days,
obtain
classic
After
and
the
test
dishes
agar
was
was
used
wells
maximum
PCA
dis-
Petrie
ml.
cutter
of
to
prepared.
1:10,000.
and
agar-gel
) in order
day
Test
( 1:2.5)
alcohol
or 7-hole
was
of
were
saturation
described
by
of
Ovary5.6
used.
Impression
Insmunofluorescence:
slide
against
the
conjugated
stain
with
Preparation
surface
globulin
Amico
were
leukemic
prepared
and
isothiocyanate
to eliminate
by
normal
dye.
nonspecific
of Gamma
Gamma
slides
of
fluorescein
was used
an
cut
gently
tissues.
pressing
Test
a
and
clean
control
Lissamine-Rhodamine
glass
sera
RB-200
were
counter-
fluorescence.4
Globulin
was
freeze-drying
prepared
by
apparatus
and
Cohn’s7
was
cold-alcohol
stored
at
+5
C.
technic.
It
in
vials
seabed
was
lyophibized
until
in
used.
Protection
Neutralization
Tests:
neutralization.
One
of
N/ml.
) and
Newborn
incubated
ICR
ml.
of
test
for
1 hour
mice
serum
at
were
was
37
used
mixed
C.
in
as
the
with
a water
0.2
test
animals
ml.
bath.
At
of
the
in
viral
end
this
study
pellet
(2.0
the
incubation
of
mg
period,
each
animal
received
0.2
ml.
of the
serum-virus
mixture
intraperitoneally.
As
controls,
the virus pellets
were
similarly
incubated
with
normal
rabbit
seruns
and
physiologic saline
solution.
Protection
Studies
of Newborn
ICR
Mice:
Newborn
animals
were
given
0.1
ml.
doses
of antibody-containing
serum
intraperitonealby
once
a day
for
3 days.
On
the
third
day
they
also
received
0.1
ml.
of virus
pellet
(0.5
fig.
N/mb.
). Other
groups
of newborn
animals
bowed
were
given
10
by
gamma
globulin
normal
rabbit
of
was
gamma
immune-tolerant
at
1,500,000
5
for
or
serum
months.
of
from
ICR
virus
saline
of
sera.
animals
fob-
This
were
dose
of
treated
with
solution.
Gamma
young
ICR
effect
intraperitoneally,
types
2 ) . Control
globulin,
mice
schedule,
protective
pellet
various
Mice:
treatment
this
the
( table
days
given
the
in
N/mi.)
derived
physiologic
was
The
cells
10
Adult
shows
ascites
mg.
continued
in Young
graph
rate
(0.5
globulin
rabbit
accompanying
survival
ml.
gamma
globulin
Studies
Protection
with
0.1
mg.
in
the
of
the
100
closes
time
gamma
mg,
of
of
obtained
10
from
mg/day.
challenge,
globulin
The
and
was
the
challenged
experiment.
RESULTS
Newborn
and
young
Splenomegaly,
to over
100,000
adult
animals
died
in 2 to 3 weeks.
animals
died
of leukemia
to 8 weeks.
this recovered
with
valescent
period
the
The
S-63
of maximal
reacted
this
differently
in
only
period,
were
20 per
demonstrated
antibodies
leukocytosis.
could
None
of the
normal
mouse
tissue
antigens.
convalescent
serum
confirmed
serum
appeared
to protect
the
of the
rest
S-63
virus.
from
50,000
The
newborn
young
recovered
adult
in 6
testing
was obtained
from
table
1. Antibodies
reacting
be
sera
cent
the
only
not
to
and leukocytosis
2 to 3 weeks.
whereas
serum
for antibody
results
are shown
in
antigen
These
mice
hepatomegaly
in both
However,
within
convalescent
group.
The
virus
animals.
bodies
against
tests
using
this
The
convalescent
ICR
lymphadenopathy,
cu.mm.
developed
in the
serum
demonstrated
showed
demonstrable
from
during
conthe
anti-
Neutralization
and
protection
the results
of the in vitro
tests.
the newborn
mouse
(table
2)
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
68
GREENSPAN
BROWN,
Table
1.-Specificity
of Antibody
Mouse
Tests
S-63
Leukemic
Mouse
Tissue
Tissue
Antigens
Mouse
Serum
of
Normal
S-63
infected0
Convalescent
MP
=
ID
=
Antigens
PCA
IF
ID
MP
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+
-
-
-
+
at
time
of
maximum
2.-Protection
Studies
on Newborn
Mice
Dead
Against
+
solution
Normal
mouse
Convalescent
S-63
serum
mouse
of
Prtcction
12/12
0
20/21
5
15/15
serum
0
4/39
90
#{176}Newbornsinjected for 3 days before, and 7 days after
3.-Protection
Studies
on Newborn
Mice
Test
Substance
Incubated
and
virus
Against
before
challenge.
S.63
Injection
Virus;
Neutralization
Test
Material
solution
Normal
Convalescent
mouse
Virus
serum
mouse
%
Protection
11/11
0
9/9
0
12/13
serum
the serum
was given
be made
inactive
by
9.2
5/21
before
and during
in vitro
incubation
Pellet
Tests
Dead
of
Leukemia
None
Saline
Virus
Tests
Leukemia
None
Saline
76.2
viral
challenge.
The virus
with
the convalescent
could
serum
3).
The
results
mune-tolerant
of antibody
to normal
leukemic
antigens
studies
of
ICR
mouse
are
shown
failed
to react
with
normal
leukemic
antigen.
Antiserum
cells or the S-63 virus
reacted
mouse
antigens
tissues.
showed
infection,
Studies
even
after
serum
obtained
tissues
and
in table
rabbits
specific
ascites
ascites
-
+
beukocytosis.
Treatment0
with
-
anaphylaxis.
In Vivo
(table
ID
immunodiffusion.
Table
when
also
IF
28
cutaneous
#{176}Serumobtained
Table
PCA
37
52
passive
=
IF
MP
microprecipitin.
=
PCA
No.
Mice
SCHWARTZ
Reaction
In Vitro
Normal
AND
adsorption
from
rabbits
subsequently
4. Antisera
from
immune-tolerant
mouse
tissues
but
did
react
produced
in normal
rabbits
with
both
normal
tissue
and
of
the
serum
against
sera
prepared
in
the
immune-tolerant
rabbit
against
with
the
against
leukemic
normal
However,
cross-protection
studies
using
immune-tolerant
that
antiascites
cell sera would
not protect
mice
against
and vice versa
(table
5).
of the protective
capability
of gamma
globulin
obtained
cell
made
imchallenged
mouse
antisera
S-63
virus
from
ascites
anticells
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
THE
S-63
MOUSE
Table
LEUKEMIA
VIRUS
4.-Specificity
69
of Antiserum
Produced
in Immune-Tolerant
Normal
Tissue
Tests
PCA
Immune-tolerant
MP
Mouse
Cell
ID
IF
S-63
Ascites
Antigen
PCA
MP
IF
++
++
++
Mouse
Leukemia
Virus
Antigen
PCA
MP
ID
IF
rabbit
antiascites
cells
anti-S-63
II.
Mouse
Antigens
Rabbits
Tests
In Vitro
-1
virus
++
+
Nonimmune-tolerant
rabbit
antiascites
anti-S-63
III.
cells
virus
++
++
++
++
++
++
++
++
++
++
++
++
+
+
+
++
+f
++
++
++
++
++
±+
++
+
Nonimmune-tolerant
rabbit
adsorbed
mal
against
tissue
-
nor-
antigen
antiascites
cells
anti-S-63
virus
Table
5.-Failure
+
-
+
+
+
-
-
+
of Cross.Protection
in Immune-Tolerant
with
Rabbits
+
±
±
Serum
-
Prepared
Tests
In Vivo
% Protection
Died
serum
Antiascites
Anti-S-63
+ S-63
serum
solution
+ S-63
Saline
solution
+ 1,500,000
in
as
accompanying
challenging
the
the
in 90 to
100
per
cent
total
of
100
mg.
of
mice
were
reverse
was
the
jective
indications
became
more
of
ascites
cells
dose.
injected
or
high.
animals
treated
more
11
10/10
0
of
of the
the
with
As might
each
passing
on
with
on the
groups
skewed,
per cent.
day, is somewhat
survival
was 80
under
20 per cent.
Protection
studies
with
globulin
in newborn
mice
time
leukemia
disease.
a half
million
of cells
produces
10 equally
of
significant
the group
of animals
treated
became
manifest,
compared
third
the
0
8/9
in 3 weeks.
in
at the
Even
0
18/18
graph.
One
and
This
number
globulin
progression
difficult
cells
ascites
virus
gamma
pretreated
of protection
12/12
1,500,000
+
Saline
are shown
were
used
to
virus
+
All
the
even
be
day.
after
The
that
the
46
per
the
it was
degree
of
of the
cent
the
possible
appearance
control
a
When
injection,
fact
expected,
received
doses.
cell
the fourth
day after
30 per cent protection
because
In the
animals
divided
is the
ascites
cells
leukemia
ob-
disease
protection
evidences
of the
of leukemia
group
started
in one of the three
two other
groups,
experimental
the survival
in
was
tected
newborn
by convalescent
animals.
mouse
S-63
virus
and
showed
(table
The
sera.
degree
immune-tolerant
6) that
this
of protection
was
gamma
similar
anti-S-63
gamma
globulin
proto that
achieved
DIscussIoN
The
develops
S-63 virus
in young
kills newborn
adult
mice
ICR
mice
generalized
in 15 to 21 days;
lymphadenopathy,
however,
there
splenomegaly,
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
70
BROWN,
Table
6.-Protection
of Antisera
GREENSPAN
of Newborn
Mice Against
Produced
in Immune-Tolerant
S-63
AND
Virus
SCHWARTZ
Means
by
Rabbits
In Viv o Tests
Dead
Treatment
None
Nonimmune-tolerant
gamma
and
globulin
anti-S-36
22/24
8.4
18/20
10.0
rabbit
globulin
leukocytosis
of 50,000
to 90,000
white
recover
blood
cells/cu.mm.
cells.
Leukemia
develops
die in 4 to 5 weeks.
The
with
a gradual
stabilization
and
previously
reported,t
demonstrable
that
___________
2/21
dominantly
of lymphoid
these
animals,
and they
animals
Protection
rabbit
Immune-tolerant
gamma
%
of
Leukemia
in
6 to
eventual
antibody
8 weeks.
made
in about
surviving
subsidence
to the
of
virus
A correlation
up
20 per
animals
abnormalities.
develops
seems
to
pre-
cent
of
recover,
As
the
in
exist
between
the
appearance
of antibody
and the drop
in white
blood
cell count.
Antibodies
obtained
from
convalescent
mice
protect
newborn
animals
the lethal
effects
of the virus
( table 2 ) The convalescent
antibodies
do
.
cross-react
adult
mice
fection
with
that
the
VltlT1
Difficulties
normal
A
tissues
from
satisfactory
mune-tolerant.
It
each
encountered
reacted
produced
against
against
animals
Antibodies
induction
of
to
test
challenge
of immune
normal
tissue
sera
with
for
the
1 ) , and
to rein-
tolerance
and
ascites
were
to
toxic
to
the
mice
( table
Furthermore,
become
to
normal
im-
tissues
antigens.
rabbits
leukemic
tissues
cells also reacted
more
tolerance.
injections
antibodies
against
4
)
against
than
the
S-63
virus
Similarly,
antibodies
normal
tissues,
and
.
antibodies
produced
in
in
animals.
parent
form
to
studies
were
carried
ascites
cell. The
in the
the
cell
against
either
produced
ascites
cell
was
obscure.
ascites
cells
in convalescent
before
out
virus
to
had
isolation
Antibodies
or S-63
mice
virus
also
determine
apparently
and
failed
failed
antigens,
and
prepared
Levi8
AKR
lymphatic
leukemia
could
a specific
antibodies
and distinct
antigen
in immune-tolerant
leukemia
cells.
he differentiated
the
relation
been
carried
the
produced
cells. This suggests
that the parent
cell is antigenically
isolated
from it. These
studies
define
3 antigens
: normal
cell
immune
leukemic
in nonimmune-tolerant
normal
the
studies
Immunologic
virus
to the
virus
the
the degree
course
of
the
before
immune-tolerant
the
in
necessary
produced
protection
inactive
is
animal
Antibodies
ICR
mice
( table
are not susceptible
from
noninfected
S-63 infection
tissues
in the rabbit.
The toxicity
of the mouse
tissue
for the
is such
that
less than
one in five injected
rabbits
survived.
method
has not been
found
for improving
the survival
rate
which
does
not compromise
not all rabbits
surviving
from
the
virus.
were
mouse
rabbit
newborn
normal
recover
from
not
antigenic
in
to cross
to react
different
tissue
the
in an
relation
of
immune-tolerant
( table 5).
the ascites
react
with
from
antigens,
to the virus.
rabbits
using
She showed
that
in
from
normal
mouse
of
the
virus
ascites
spontaneous
this system
antibodies
to
(AKR)
tissue
antigens.
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
S-63
THE
The
LEUKEMIA
MOUSE
antibodies
recipient
produced
mice,
were
leukemic
antibodies
antibodies
therapeutic
in
a finding
Experiments
of
71
VIRUS
immune-tolerant
we
also
performed
rabbits
observed
in the
in order
produced
were
administered
potential.
One
in
to determine
at various
stages
and a half million
of leukemia.
Mice
receiving
showed
minimal
protection.
antibody
ment
has
within
chance
relation
to two
the
after
the
to
to
)
1
effect.
The
.
evaluate
leukemia
their
in 90
mg. of gamma
globulin
from
to resist
the
doses
of normal
rabbit
time
of administration
appearance
the
capability
( fig.
were
given
100
receiving
gamma
strong
capability
to its protective
days
protective
rabbits
of infection
cells
produced
similar
The
toxic
Pretreatment
of
or
of symptoms
gave
gamthe
treat-
the
best
of survival.
Protection
duced
the
a decisive
one
not
system.
immune-tolerant
to 100 per cent of young
ICR mice.
The mice
globulin
derived
from
various
sources.
Those
immunized
immune-tolerant
rabbits
showed
development
ma globulin
were
5-63
studies
in
with
convalescent
immune-tolerant
development
of
leukemia.
of
antibody,
time
of
Several
explanations
progress
of the disease
studies
amount
against
the
of gamma
(2 )
from
the
ascites
cells
showed
The
amount
recipient.
ing the
gate
freely;
of surviving
mouse
rabbits
degree
treatment,
are possible
after
the
cells : ( 1
available,
ascites
globulin
leukemic
cells;
changes
(3 )
to perpetuate
or
such
of
with
antibodies
antibodies
modification
pro-
can
modify
depends
on
the
and
toxicity
of the antibody
to the
regarding
the difficulties
in reversthird
day of symptoms
in protection
the ascites
allowing
cells
other
neutralize
the limited
ascites
cells
to propa-
progress
because
of sufficient
“autonomy”
is released
in sufficiently
large
quantities
virus
the
)
sera,
that
progress
of the
infection.
SUMMARY
The
present
sponse
of
studies
mice
to
are
an
designed
to show
whether
determinations,
and whether
produced
in immune-tolerant
studies
in
mice
were
immunodiffusion,
antigens
and
extension
of earlier
a leukemogenic
a correlation
protective
animals.
compared
antibodies.
passive
and
As
shown
.
on
These
the
antibody
re-
investigations
were
exists
betveen
in vivo
and in vitro
antibodies
against
the virus
could
be
Viral
neutralization
and
protection
with
microprecipitin,
reports
( S-63 )
virus
cutaneous
in
tables
( PCA),
anaphylaxis
immunofluorescent
tests
1, 2 and
3,
using
antibody
similar
could
be
demonstrated
by both
in vivo and in vitro
methods,
and these
studies
showed
(table
2) that the antibody
was protective.
The
S-63 leukemia
virus
was
isolated
in 1963
from
a mouse
ascites
cell
leukemia
line.
That
cell line had
been
carried
in the laboratory
for over
3
years.
studies
The virus
has
were
carried
originating
against
been
out
ascites
the
S-63
cell.
virus
carried
in ICR mice
since
its isolation.
to determine
the relation
between
the
Studies
were
Antibodies
do
produced
not
cross
react
in
antibodies
unsatisfactory
because
of cross
reaction
with
have
yielded
valuable
information:
virus
of
normal
for
mouse
immune-tolerant
against
intact
produced
purposes
tissue.
rabbits
ascites
in
cells
of
Immunologic
virus
and
normal
these
experiments
Immune-tolerant
injected
from
which
the
rabbits
animals
with
the
S-63
the
virus
was
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
72
BROWN,
Injection
of
ascites cells
1,500,000
GREENSPAN
SCHWARTZ
AND
GROUP
Control
0%
In-
.
0%
-3
0
Days
cell
5
_________
V
-
Symptoms
.
.
+10
#{149}:v
inrelationto
injection
vJI.
i’)$
Rabbit
c’’i
Nor moi
10mg
/day
Gamma Globulin
Immune-tolerant
Gamma Giobuj
I
nil:
I
I
I
5
10
Day in relation
Fig.
1.-Protection
originally
isolated.
cells
Antibodies
tect
mice
induced
antiascites
with
against
by
to
produced
Le
protect
hic-reportate
newborn
virus
from
le
producite
de
e del
tests
cipitina,
Le
de
e de
datos
tabula
2-le
Le
virus
laboratorio
vitro
con
contra
de
ascites
durante
pro-
disease
with
best
either
time
at the
develop
in adult
produced
to those
esseva
Ille
murin.
que
etiam
in
linea
3 annos.
inter
del
neutralisation
esseva
esser
comparate
de
antigenos
que
relative
Le in-
pote
immunodiffusion,
vitro
.
correlation
muses,
simile
un anticorpore
S-63
plus
de
)
le virus
Studios
in
1, 2, e 3 indica
como
reportos
( S-63
un
anti
effectuate
utilisante
esseva
leucemia
si il existe
cutanee,
in tabulas
vivo
anticorpore
de
the
and
treated
disease.
The
infection
immunologic.
ilbo,
anaphylaxia
in
the
cells
against
cells
the
e si anticorpore
immunofluorescentia
tanto
ascites
not
de previe
leucemogenic
virus
determinar
tolerantia
protection
summarisate
demonstrate
leucemia
pro
e in
extension
contra
concipite
passive
against
against
INTERLINGUA
un
muses
vivo
animales
in
virus
con
in
globulin.
produced
from
00%
months
leukemia.
These
antibodies
the standpoint
of protection,
IN
representa
de
esseva
five
rabbits.
studios
observationes
80
at
treatment
is started
of the disease.
animals
from
S-63
are similar,
anticorporee
vestigationes
similarly
antigen.
rabbits
ascites
against
when
stages
60
survival
gamma
Mice
challenged
with
globulin
are protected
in immune-tolerant
responsa
rabbit
but
SuIIAmo
al
40
cent
leukemia,
therapeutic
advantage
is obtained
of cell inoculation
or in the early
which
20
Per
antibodies
cell-induced
5-63 virus.
cell gamma
Antibodies
0
against
the virus
in immune-tolerant
ascites
ICR
mice
recovering
by convalescent
mice
15
st symptoms
immune.tolerant
Conversely,
do not react
produced
ascites
-l
ix
micropre-
e anticorpores.
anticorpore
poteva
e que-vide
esser
specificamente
protective.
isolate
cellular
Le
in
1963
ab
habeva
virus
habeva
un
essite
linea
de
mantenite
essite
portate
cellulas
in
be
per
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
S-63
THE
MOUSE
muses
ICR
determinar
del
LEUKEMIA
depost
be relation
anticorpore
be objectivos
cruciate
ha producite
Le
con
cellulas
ab
de grande
Anticorpore
producite
ascites
protege
muses
non
de
ascites
contra
contra
be morbo.
mento
es
Le
le precoce
stadios
optime
del
per
essite
post
contra
isolate
contra
virus
S-63.
anti
injec-
be intacte
origmnalmente.
le cellulas
Muses
cellulas
therapeutic
del
phenomeno
immuno-
de ascites
viral.
gamma
effecto
made-
contra
cellulas
cellulas
de ascites
provocate
per
de
es protegite
ascites
es obtenite
inoculation
de
cellulas
quando
cellulas
o al
le
minus
tractadurante
morbo.
capace
a proteger
animales
‘eboppa
in adulte
muses
ICR
S-63. Iste anticorpore
producite
durante
per
puncto
protectori,
de vista
habeva
be antigeno
al tempore
Anticorpore
cruciate
similemente
gbobulina
pro
Studios
esseva
immunologic
reaction
be virus
inducite
con
initiate
S-63
in conilios
a tolerantia
immunologic
contra
leucemia
a induction
per
be morbo
e tractate
be virus
a tolerantia
producite
contra
immunologic
de ascites.
in consequentia
del
Animales
a tolerantia
nulle
le quales
reaction
contra
studios
cellulas
valor:
conilios
monstrava
anticorpore
nulle
normal
experimentos
tissu
murin.
in
5-63
ascites
monstrava
sed
iste
normal
producite
Conversemente,
de
de
con
be virus
de
in conilios
information
anticorpore
tiones
isolation.
Esseva
effectuate
inter
le virus
e su originatori
producite
quate
pro
de reaction
logic
su
73
VIRUS
de br
effecto
neonate
contra
be infection
br restablimento
ab
muses
in convabescentia
a illo
producite
se
leucemia
per
es simile,
in conilios
disvirus
ab be
a tolerantia
immunologic.
ACKNOWLEDGMENT
We
acknowledge
University
of
our
Illinois
indebtedness
School
of
to
Dr.
Medicine,
for
Peter
his
Buinauskas,
Department
invaluable
of
Surgery,
assistance.
REFERENCES
1. Greenspan,
Schwartz,
I.,
202:916,
Garb,
in
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and
Stein,
rabbits
of
of
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Garb,
R.,
and
Allergy
response
of
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Nature
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mixture
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E.
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to a leukemogenic
mice
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Brown,
S.,
Proc.
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A.
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of
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Sims,
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experimental
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of
Derouaux,
C.,
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quantity
mt.
Arch.
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ture
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ration
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of
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the
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degree
speBlood
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cutaneous
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Barnes,
J.
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tleman,
1963.
Z.:
1958.
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and
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the
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in
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to
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and antibody.
1959.
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72:465,
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activity
Na-
From www.bloodjournal.org by guest on January 20, 2015. For personal use only.
1966 27: 65-73
Antigenic Behavior of the S-63 Mouse Leukemia Virus
ERIC R. BROWN, IRVING GREENSPAN and STEVEN O. SCHWARTZ
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