MODIFICATION OF RUNT DISEASE 375 



fifth day. This has not been interpreted as evidence against the 

 "exhaustive sensitization" concept advanced by Simonsen (i960) 

 who has presented evidence that adult spleen cells transferred to 

 Fj hybrids between the donor and an unrelated strain are rapidly 

 and specifically rendered incapable of reacting against their 

 host. This view has since been supported by the findings of 

 Dineen (1961) who was largely unable to transfer runt disease to 

 secondary recipients even though they were found to contain 

 donor antigens. If we enlarge our considerations to include 

 radiation chimeras, findings of similar import by Cole and Davis 

 (1961) can be included. These authors demonstrated that cells of 

 donor origin in long-lived radiation chimeras can be specifically 

 incapable of reacting against host antigens. The protracted course 

 of runt disease in some strain combinations and the long delayed 

 onset of secondary disease after irradiation and homologous bone 

 marrow transfer, taken with the present findings, make it unlikely 

 that a high proportion of the donor's ability to react to the host 

 is very promptly destroyed or inactivated. From the evidence 

 available it would appear, however, that graft-versus-host reac- 

 tivity often gradually disappears. 



Indeed, this phenomenon may help to explain the response of, 

 for example, a "conventionally tolerant" mouse to skin grafts 

 from certain third strains. As Billingham and Brent (1959) 

 found, and we have confirmed, A-line mice made tolerant of 

 CBA skin grafts by the neonatal injection teclmique will reject 

 C3H skin grafts, but not in the usual 10 to 11 days characteristic 

 for C3H grafts on normal A-line recipients nor the 12- to 13 -day 

 period expected of C3H grafts on normal CBA mice. Instead 

 such C3H grafts are rejected after 20 to 25 days. Sharing of 

 antigens between C3H and CBA inight account for a relative 

 reduction in reactivity of the indigenous or A-line components of 

 the chimeric animal's lymphoid system, and some reduction in 

 cell number consequent to a mild graft-versus-host reaction may 

 account for an additional amount of depression. The CBA 



