TRANSPLANTATION TOLERANCE AND 

 IMMUNITY IN RELATION TO AGE 



J. G. Howard, Donald Michie and M. F. A. Woodruff 



Department of Surgical Science, University of Edinburgh, and the Medical Research 

 Council Research Group on Transplantation 



Immunological tolerance to transplanted tissues was first 

 discovered as a state acquired during foetal or early neonatal life. 

 This circumstance, together with the prevailing idea that the 

 faculty of immune response does not mature until some time after 

 birth, led the early workers (Billingham, Brent and Medawar, 

 1956; Hasek, 1956) to propose a scheme along the following hues: 



Developmental stage Characteristic modality 



of presumptively of immunological 



immimological tissues response 



(i) "Adaptive phase" Tolerance 



(2) "Null" or "neutral" Nil 



period 



(3) Maturity Immunity 



The underlying idea may be termed the "qualitative 

 hypothesis", since a change in kind is presumed to overtake the 

 immunological system during early life. The alternative, or 

 "quantitative", hypothesis envisages only a change in degree^ and 

 places the induction of tolerance by foetal or neonatal exposure 

 to antigen in the same category as the immunological paralysis 

 which Pel ton (1949) was able to induce in adult mice. 



Two hues of work in our department have recently yielded 

 independent and complementary supports to the latter hypothesis. 

 In the first place, Michie and Woodruff (1962) have induced a 



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