M. KENT 



effects on tlieir homologous neighbours has been demonstrated by in vitro 

 tissue cultures, 



METHODS OF PROLONGING HOMOGRAFT SURVIVAL 



Using the theory of actively acquired immunity as a working hypothesis, 

 attempts at homograft prolongation have followed these lines: — 

 {]) 'Desensitization' of the proteins of the homograft before application. 

 The limitations of this approach are apparent. 



(2) Isolation of the graft from contact with the host's antibody-producing 

 mechanisms — the success of anterior chamber grafts is an example of this 

 approach. 



(3) Modification of the activity of the reticulo-endothelial system of the 

 host. Methods used include mechanical blockage by intravenous injections 

 of trypan blue, nitrogen mustards, total body irradiation and steroid 

 administration. 



(4) The phenomenon of 'actively acquired tolerance '2. Tissue inoculation 

 before, or at birth, from another animal of the same species, will allow a 

 host to accept, later in life, grafts from the original donor. This effect seems 

 to depend on some kind of 'training' of the cells which undertake immuno- 

 logical reactions, while the cells are still immature. 



Much interest has centred on the effects of total body irradiation on graft 

 survival, and many workers, both in Britain and the U.S.A., are engaged 

 in this field. Dempster et al.^ reported prolongation of skin graft survival 

 to 16 to 20 days, using sub-lethal doses of irradiation, but after this period 

 there was rapid rejection of the graft. The effect was increased with higher 

 X-ray dosage, but lethal levels were reached before prolongation of the 

 acceptance of the graft was apparent. 



Methods have been sought to allow survival of animals while X-ray 

 dosage is increased to still higher levels. Blood transfusions have a transient 

 effect. A more prolonged effect (offering protection of one to three months) 

 is afforded by injection of homologous bone-marrow extracts^, whilst if 

 isologous marrow {i.e., transplantation within an inbred strain) is used, the 

 effect appears to be permanent^ Splenic-pulp injections have a similar 



effect". 



Jacobson' was able to protect mice, following whole-body lethal irradi- 

 ation, by this means, and many have confirmed this experiment. Workers 

 at Harwell^ have demonstrated that this protection is due to colonization 

 of the host's bone marrow and lymphoid tissue by marrow cells of the donor, 

 the identification of the donor's cells being made possible by altering their 

 chromosome pattern. Similar success in protection against the lethal effects 

 of irradiation by bone-marrow injection has been demonstrated in the 

 rabbit^ and the dog^", whilst there are some reports of success with hetero- 

 logous marrow^ ^. 



Under these circumstances, before recovery of the reticulo-endothelial 

 system of the host occurs, homografts from genetically related mice have 

 been shown to survive^^. Trentin^^ demonstrated tolerance of homografts 

 from the donors of the bone marrow, in mice, both with isologous (genetically 

 related) and homologous mice, but found no prolongation of the homograft 

 reaction if the bone marrow and the skin were taken from different animals, 

 fi 69 



