TRANSPLANTATION TOLERANCE AND AGE I49 



to be elucidated. In particular the methods used could profitably 

 be checked against independent criteria of immunity, such as skin 

 grafting. Perhaps even more urgent is a more detailed characteri- 

 zation of the specificity of the effect. Preliminary studies in which 

 irradiated ASW spleen cells were injected into A newborns, 

 followed by challenge with CBA spleen cells, have substantiated 

 the specificity of the phenomenon. But it is too early to say 

 whether or not a non-specific component is also involved in the 

 reaction. 



In summary, the evidence as it stands has brought to light a 

 novel phenomenon which it is tempting, to say the least, to inter- 

 pret as immunity to homologous cells induced in the newborn by 

 exposure to histocompatibihty antigens. 



Discussion 



Although many past attempts to detect immunity following 

 foetal or neonatal exposure to antigen have failed, homograft 

 immunity in the foetal sheep was demonstrated by Schinkel and 

 Ferguson as long ago as 1953. Three more recent successes may 

 be quoted. Uhr, Dancis and Neumann (i960) elicited delay ed- 

 type hypersensitivity in the premature human infant; Rees and 

 Garbutt(i96i) conferred resistance to Mycobacterium tuberculosishy 

 vaccination of 15-17 day foetal mice; and Silverstein, Kraner and 

 Lukes (1962) provoked the formation of non-specific and specific 

 y-globulins by administering BCG, salmonella and ovalbumin 

 to 90-day foetal sheep. These latter investigations were concerned 

 only with heterologous antigens, and it has been suggested by 

 Billingham, Brent and Medawar (1956) that the acquisition of 

 immunological reactivity to heterologous antigens may occur 

 earlier in development than to homologous antigens. Yet the 

 fact that foetal sheep, and, as we have shown, newborn mice can 

 react also against homologous antigen renders this idea unneces- 

 sary. We should rather discuss the observation which prompted 



TRANS. — 6 



