TRANSPLANTATION TOLERANCE AND AGE 139 



State of Specific unresponsiveness to skin homografts in adult 

 mice and have shown that this state bears all the hallmarks of 

 tolerance in the sense originally defined by Medawar and his 

 colleagues. In the second place, Howard and Michie (1962) have 

 found it possible to immunize newborn mice with preparations 

 of the same homologous cells which in higher dose will induce 

 tolerance. 



Tolerance in adults 

 In the past year or two many workers have induced in adult 

 mice states of specific unresponsiveness to skin homografts by 

 massive preliminary infusion of the intended recipient with donor 

 cells, both by parabiosis and by repeated injection procedures. 

 These demonstrations fall short of proving the induction of 

 immunological tolerance, by reason of the following possibilities: 



(i) The host's immunologically competent cells might be totally 

 replaced by cells of donor origin, as commonly occurs in radiation 

 chimeras. 



(2) The host's immunologically competent cells might be 

 rendered entirely inert under the impact of the antigenic over- 

 load, the host's immune functions, as in case (i) above, being 

 taken over by cells of donor origin. 



(3) The host's immunologically competent cells might retain 

 their functions, but exercise them in a manner protective of the 

 graft, namely by the production of enhancing antibodies. 



These objections have all been circumvented in Simonsen's 

 (i960) demonstration of the acquisition of specific tolerance by 

 grafted adult lymphoid cells of parental-strain origin towards 

 Fi hybrid hosts into which they have been inoculated. While 

 logically compelling, his experiments present a feature so astonish- 

 ing as to justify a certain hesitation in accepting their fuU impli- 

 cations. The donor cells appear to acquire tolerance of the host 

 tissue within 24 hours of inoculation, and yet already in this short 

 period to have mounted and given final effect to an immune attack 



