IMMUNOLOGICAL COMPETENCE OF SMALL LYMPHOCYTES 26l 



from single cells that suffer loss or inactivation of histocom- 

 patibility genes. Such cells are assumed to react against normal 

 cells possessing the relevant antigen(s) as in experimental graft- 

 versus-host reactions. The precancer cell is supposed to respond 

 to the proliferative stimulus of the new foreign, "host" antigen 

 v^ith the result that cancer cells gradually destroy and replace 

 normal ones. If this hypothesis has general validity, one would 

 expect that animals which escape lethal transplantation disease 

 should later show a high incidence of tumours. We found no 

 evidence of cancer in our runt disease survivors, but these animals 

 were not kept sufficiently long to make negative results con- 

 vincing in this connexion. The idea of a prohferative stimulus to 

 "graft" cells by "host" antigens is of course in accord with 

 clonal selection theory. The present results merely argue against 

 the necessity for such cell prohferation as a requirement for 

 transplantation disease. 



Summary 



Purified preparations of small lymphocytes derived from adult 

 C57BL/6 blood were found capable of producing transplantation 

 disease in newborn A/Jax and in very young F^ (C57BL x A) 

 hybrids. About 900,000 small lymphocytes constituted a threshold 

 dose for the induction of fatal disease. Over the dosage range of 

 o* 9-2*0 milhon lymphocytes, there was no substantial difference 

 in the severity of the disease syndrome. The median survival time 

 for A/Jax mice after injection of 0-9-1 -5 million and 2 million 

 small lymphocytes was 16-4 (15 •4-17- 5) days and 17*4 (15*6- 

 19 '6) days, respectively. However, injection of lymphocytes 

 from preimmunized donors led to accelerated transplantation 

 disease with a median survival time of only 10 -8 (9- 2-12- 7) 

 days. This fmding strongly supports the contention that the 

 lymphocyte-mediated syndrome has a primary immunological 

 basis. 



