IMMUNOLOGICAL COMPETENCE OF SMALL LYMPHOCYTES 257 



hybrids inoculated with spleen cells from isoimmune A-strain 

 donors may be related either to the use of very large doses of 

 immune donor cells, the adult status of the recipients, or both. 

 A more detailed account of the histopathological changes 

 induced by small lymphocytes will be reported elsewhere. 



The chief difference in our interpretation of graft-versus-host 

 reactions is that host cell multiphcation is held responsible for the 

 organ enlargement and accentuated splenic erythropoiesis, 

 whereas the pathological lesions result from the immune reactivity 

 of small donor lymphocytes with a long hfespan. On this premise, 

 the proliferation and intervention of descendants of donor cells 

 are not required for the development of the runting syndrome. 

 That blood lymphocytes normally survive for several or many 

 weeks, rather than for just a few hours or days as previously 

 supposed, has been shown in various recent studies (Hamilton, 

 1958; Trowell, 1958; Gowans, 1959). 



The acquisition of lasting tolerance by A/Jax newborns 

 inoculated with foetal C57BL/6 hver cells without concomitant 

 transplantation disease demonstrates that tolerance does not 

 depend upon widespread destruction of host lymphoid tissue. 

 Conversely, the absence of tolerance and chimerism in A/Jax 

 survivors of runt disease mediated by adult C57BL/6 small 

 lymphocytes supports the assumption that these lymphocytes are 

 end cells that leave no descendants in the host. One could 

 also attribute the failure of immunologically active C57BL cells 

 to persist in A/Jax recipients to injury in a highly foreign antigenic 

 environment (Boyse, 1959) or to exhaustive sensitization (Simon- 

 sen, i960). However, any transplanted cells or their descendants 

 that lacked immunological reactivity should have survived 

 indefmitely in compatible hosts. Earher evidence that runt disease 

 requires host tolerance, but that tolerance of the graft does not 

 depend upon trauma to the host, has been summarized by 

 Billingham (1958). 



Thefmdingthat75percentofFi(C57 x A) hybrids, inoculated 



