362 PAUL S. RUSSELL 



cells are given intravenously immediately after the homologous 

 cell injection by another vein, indicating that their effect does not 

 depend upon intimate contact before administration. No attempt 

 was made to quantitate the dose of cells required for the protective 

 effect, although the system might be expected to lend itself well 

 to this in a maimer similar to Winn's (i960) use of a parallel 

 experimental design where sensitized cells are mixed with tumour 

 cells before transfer. Later skin grafts applied to the survivors 

 were rejected in an entirely normal fashion with no suggestion 

 either of specific tolerance or of sensitization. 



Delaying the protective injection until two days later, or the 

 third day of hfe, reveals a difference between the rapidity of 

 effectiveness of normal as compared to presensitized cells. Fig. 10 

 combines the resuhs obtained in the treatment of three litters of 

 C57BL/6 animals all of which received more than 10 million 

 DBA/ 1 spleen cells intravenously on the day of birth. Two days 

 later approximately 15 million adult C57BL/6 spleen cells were 

 given, again intravenously, 4 animals receiving cells from donors 

 which had previously rejected DBA/i skin grafts and 5 from 

 normal donors. Although a virtually normal weight-gain curve 

 follows the adoptive transfer of sensitized cells the delay in onset 

 of normal development after the protective injection of normal 

 cells suggests a transient influence of the primary inoculum which 

 is only overcome when the second wave of adult cells reaches an 

 appropriate level of activity. This difference in rate of effective- 

 ness is quite reminiscent of that noted by Billingham, Brent and 

 Medawar (1956) in the time required for rejection of previously 

 tolerated skin grafts by mice receiving normal as against previously 

 sensitized isologous lymphoid cells. 



When the second intravenous injection is postponed two days 

 longer to the fifth day of life, unscnsitized cells have in no instance 

 been sufficient to overcome the damaging effects of the initial 

 injection. Even the use of cells from donors highly sensitized, as 

 described above, will not release mice under these conditions from 



