I 
EXTRACORPOREAL IRRADIATION OF BLOOD AND LYMPH 
D. D. Joel and E. P. Cronkite* 
j Methods have been developed for continuous or inter- 
mittent extracorporeal irradiation of circulating blood 
(ECIB) and thoracic duct lymph (ECIL) in calves and 
' goats. ECIB and ECIL both induce a marked and sus- 
tained lymphopenia as well as a decrease in the thoracic 
duct lymphocyte output and a depletion of an easily 
mobilizable pool of lymphocytes from lymphoreticular 
I organs. A significant pool of sessile lymphocytes is un- 
affected by these procedures. 
The functional aspects of the mobilizable pool of cells 
have been tested by challenging ECIB or ECIL treated 
j animals with tetanus toxoid and/or orthotopic allo- 
grafts. The primary and secondary antibody responses 
to tetanus toxoid were only slightly repressed by pre- 
treatment with either repetitive ECIB or continuous 
ECIL. Repetitive ECIB given prior to grafting will 
prolong skin allograft acceptance time 2 to 3 days. 
Further graft survival was obtained, however, when 
ECIB was continued following grafting. With continuous 
I ECIL skin allograft survival was dependent upon the 
location of the graft. As with skin grafts, kidney allo- 
graft survival time was longest in animals treated with 
ECIB both before and after transplantation. 
INTRODUCTION** 
Extracorporeal irradiation was apparently 
first conceived of as early as 1921,i however, it 
received little attention until the early 1960's. 
The development and use of extracorporeal ir- 
radiation as a method to deplete the body of 
lymphoc5d;es for purposes of studying various 
aspects of cell physiology in normal and leu- 
kemic calves has been described in detail in a 
series of publications from the Brookhaven Na- 
j tional Laboratory. 2-12 in this report we will 
briefly review the methods used, and their effect 
on lymphoid tissues and immune responses, 
particularly transplantation immunity. 
The underlying principle of extracorporeal 
irradiation is to utilize the difference in suscep- 
tibility to injury by irradiation between circulat- 
i ing lymphocytes and other formed elements in 
I • Medical Research Center, Brookhaven National Laboratory, 
Upton, New York. 
** Work supported by the U.S. Atomic Energy Commission. 
blood or lymph, i.e., doses which are lethal to 
the vast majority of lymphocytes are relatively 
harmless to red blood cells, neutrophils and 
platelets. In practice, two experimental ap- 
proaches have been developed. The first, extra- 
corporeal irradiation of blood (ECIB), is ac- 
complished by diverting a fraction of the 
cardiac output through a radiation field by 
means of a semipermanent carotid artery-jug- 
ular vein shunt composed of Teflon and Silas- 
tic" (Figure 1). During ECIB, cells within the 
blood accumulate a dose of radiation as they 
pass one or more times through the irradiator. 
The amount of radiation received by a cell dur- 
ing one circuit past the radiation source is re- 
ferred to as the transit dose (transit doses 
ranging from 15 to 1,500 rads have been used in 
various studies). When a lethal dose is attained 
the cell is removed from the circulation by the 
reticuloendothelial system. Although ECIB can 
be given continuously or in short repetitive 
sessions, there is a limit on the total amount of 
ECIB which can be tolerated within a given pe- 
riod of time. This limit is determined by the ac- 
cumulated dose to the red blood cells which, 
because of their relatively long intravascular 
life span, may make several transits through 
the radiation field.* In calves, red cells can 
accumulate up to 50,000 rads before hemolysis 
begins,^'' while in goats the tolerable dose is 
much lower i.e., about 10,000 rads. For this 
reason and other considerations pertaining to 
exchange of lymphocytes between various tis- 
sue and circulating pools, daily repetitive ECIB 
is preferred over continuous ECIB. 
The second experimental approach which has 
been developed is extracorporeal irradiation of 
lymph (ECIL). In this system thoracic duct 
lymph is simply diverted through the radiation 
field using Teflon-Silastic shunts.^^ Because of 
the low hydrostatic pressure of efferent lymph. 
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