894 
GENETIC AND BIOLOGICAL EFFECTS OF RADIATION 
EFFECT OF ECIB AND ECIL ON 
IMMUNE RESPONSES 
Antitoxin Response 
The effects of extensive repetitive ECIB and 
continuous ECIL on the primary and secondary 
antitoxin responses in calves to stimulation by 
tetanus toxoid have been published."'^^ Al- 
though the appearance of detectable serum anti- 
body was delayed 5 to 10 days and peak titers 
were slightly reduced, all calves gave nearly 
normal primary responses despite the severe 
depletion of lymphocytes in the circulating 
blood and thoracic duct lymph. This is in con- 
trast to the findings of McGregor and Gowans 
in rats depleted of lymphocytes by drainage of 
the thoracic duct for 5 days. It should be empha- 
sized that in the rat experiments fluid toxoid 
was given by intraperitoneal injection, whereas 
the calves were immunized with a subcutaneous 
injection of either aluminum phosphate ab- 
sorbed toxoid^" or fluid toxoid.-" Antigenic 
stimulation by intraperitoneal injection relies 
heavily on splenic participation as compared 
to regional lymph nodes. As shown above, the 
spleen was depleted to a much greater degree by 
ECIB than were lymph nodes. If the same is 
true for thoracic duct drainage in the rat one 
might anticipate greater immunosuppression to 
systemic immunization. The effect of ECIB 
and/or ECIL on systemically administered an- 
tigens has not been tested. Antigenic dose per 
kg body weight, which was much higher in the 
rat experiments, may also be important partic- 
ularly in lymphocyte depleted animals. Exten- 
sive repetitive ECIB also failed to signiflcantly 
repress secondary responses to fluid tetanus 
toxoid. 
Skin Allografts 
Repetitive ECIB given prior to skin grafting 
prolonged the graft acceptance time by 2 or 3 
days and changed the normal violent skin allo- 
graft rejection to more chronic, milder reac- 
tion. As a consequence of the severe lympho- 
penia, cellular infiltration into the graft bed 
was markedly reduced. When repetitive ECIB 
was continued after grafting, the acceptance 
time was further prolonged. Of special interest 
is the observation that ECIB was most effective 
in prolonging skin allograft survival when used 
in combination with small doses of azothioprine 
( Imuran f^^i) which themselves had no effect on 
rejection. This suggests that ECIB and im- 
munosuppressive therapy may be synergistic. 
Thymectomy combined with ECIB was no more 
effective than ECIB alone.^^ 
The effect of continuous ECIL on skin allo- 
graft rejection is somewhat different. Prolonged 
ECIL (10-22 days) prior to grafting resulted 
in a 5 to 8 day prolongation of graft survival 
which was slightly better than that achieved 
by pregraft ECIB. When ECIL was continued 
after grafting, graft survival became dependent 
upon the anatomical location of the grafts. 2* 
The probable explanation for these findings are 
schematically shown in Figure 7. Following the 
transplant of a histo-incompatible skin graft, 
committed lymphocytes ("killer cells") are pro- 
duced in the regional lymph node, presumably 
through antigenic stimulation and cell division. 
These cells enter the blood via the efferent 
lymphatics and return to the graft site where 
they effect rejection. It can be seen that, whereas 
ECIB will destroy only a fraction of cells enter- 
ing from the efferent Ijonph, ECIL will affect all 
such cells provided the skin graft is placed 
within the drainage bed of the efferent lymph 
being irradiated. In the case of ECIL, all ef- 
ferent lymph from the posterior part of the 
body enters the thoracic duct and passes 
through the irradiator. Thus when ECIL is 
continued following grafting, posteriorly placed 
skin grafts will survive for the duration of 
ECIL while skin grafts on other parts of the 
body (anterior grafts) will be rejected, pro- 
vided that: (1) lymphatico-venous communica- 
tions other than the thoracic duct are absent; 
and (2) anterior and posterior grafts are from 
two unrelated donors. The results are shown in 
Table I. It is of interest that postgraft ECIL 
also extended the survival of anterior grafts, 
suggesting that committed cells recirculate 
through the thoracic duct and are thus destroyed 
by ECIL. These experiments demonstrate that: 
(1) viable cells emerging from regional lymph 
nodes are essential for skin allograft rejection 
and these cells are susceptible to injury by ir- 
radiation; and (2) entry of committed lympho- 
cytes into the blood is obligatory via the efferent 
