Studies on homografts of foetal and infant skin and further observations on the anomalous properties of pouch skin grafts in hamsters

Abstract

A systematic study has been made of the influence of donor age on the survival of skin homografts in Syrian hamsters. Estimates of the MSTs (in days) of adult skin homografts exchanged between adult members of three different isogenic strains were: MHA $\rightarrow $ CB, 11$\cdot $9$\pm $0$\cdot $7; CB $\rightarrow $ MHA, 11$\cdot $2$\pm $0$\cdot $5; CB $\rightarrow $ LSH, 11$\cdot $5$\pm $0$\cdot $4 (section 4.1). The MSTs for grafts of neonatal skin for these three combinations were: 21$\cdot $6$\pm $2$\cdot $4; 16$\cdot $0$\pm $1$\cdot $5; and 15$\cdot $2$\pm $1$\cdot $7, respectively, indicating that donor age is an important determinant of homograft survival in this species (section 4.2). With the MHA $\rightarrow $ CB combination, where the influence of age is most striking, it was found that the MST of grafts from even 30-day-old donors (16$\cdot $7$\pm $1$\cdot $3) is still significantly greater than that of adult skin grafts. With the other two combinations the influence of variation in donor age is restricted to the first few days of life (section 4.2). The MSTs of grafts of neonatal F$_{1}$ hybrid donor's skin closely resembled those of grafts of similar age from donors of the corresponding parental strains, thus providing no evidence for a gene-dosage effect (section 4.3). Three hypotheses which might account for the observed superior longevity of neonatal skin homografts are as follows: (i) they are less susceptible to sensitivity than grafts from older donors; (ii) they are immunogenically inferior to older grafts; and (iii) they may exert some kind of specific weakening influence on their host's ability to develop homograft sensitivity (section 5). Experiments designed to evaluate these hypotheses (section 5.1 to 5.4) have yielded strong evidence in favour of (ii), though they do not exclude trivial contributions from (i) and (iii). The more important findings bearing upon these possibilities are (a) Neonatal skin homografts display normal susceptibility to pre-, concurrent or subsequent specific sensitivities elicited in their hosts by proxy (section 5.1), and (b) Neonatal skin homografts curtail the survival of concomitantly transplanted grafts of 'immunologically privileged' cheek pouch skin of similar genetic origin to a much lesser extent than skin grafts from adult donors (section 5.2). In the course of this analysis it has been found that acceptance of homografts of cheek pouch skin for upwards of 50 days usually results in the total abolition of the host's ability to reject subsequent grafts of neonatal skin from the same donor strain (section 5.2). Failure to prolong the survival of skin homografts by pretreatment of their hosts with lyophilized tissues from the donor strain (section 5.4) suggested that the principle of immunological enhancement does not apply in hamsters, probably because of their apparent reluctance to produce humoral isoantibodies. Accordingly, it was provisionally concluded that pouch skin homografts may chronically release isoantigenic material, probably directly into the blood stream, in a form appropriate to induce a state of transplantation tolerance (section 6). That this tolerance is only partial is indicated by the finding that homografts of adult skin transplanted to long-term acceptors of pouch skin are rejected with almost normal promptitude and the sensitivity evoked destroys the hitherto accepted pouch skin grafts. The thesis is discussed that vascularized solid tissue homografts that are incapable of sensitizing their hosts-as for example, when they are placed in immunologically privileged sites-may progressively induce transplantation tolerance (section 6).