Skin Homografts: Tolerogenic Versus Immunogenic Influences in Mice

Abstract

In strain combinations involving multiple non-H-2 disparities, neonatal skin grafts may survive significantly longer than adult grafts of similar genotype on normal adult hosts, and repeatedly outlive grafts of adult origin on immunosuppressed recipients. Moreover, newborn grafts of long-standing may render their hosts unresponsive to adult skin grafts from the same donor strain. With some H-2-compatible strain combinations in which homozygous neonatal grafts are rejected, F1 hybrid (heterozygous) grafts of similar age not only may survive indefinitely, but also may induce tolerance of subsequent adult parental strain homografts. These tolerogenic and gene dosage effects, although much weaker, can likewise be revealed with H-2-incompatible neonatal skin grafts.

The Role of Passenger Leukocytes in the Anomalous Survival of Neonatal Skin Grafts in Mice

“…7 days later, these secondary hosts were challenged contralaterally with adult C3H skin grafts. The MST of these test grafts was 7.8 days, contrasting significantly (P < 0.001) with the MST of 10.7 days for adult C3H skin grafts on naive strain A recipients (9). Apparently, the C3H grafts were rejected in accelerated fashion because their hosts had been sensitized by adult leukocytes of (C3H X A)F~ origin which the fetal isografts transported from their intermediate tolerant hosts.…”

“…Whereas current reports have established that passenger leukocytes contribute to the immunogenicity of the skin grafts bearing them (21,22,29,30,32,33), it is evident from the present study that passenger antigens (most probably in the form of leukocytes) contribute also to the induction of tolerance by neonatal skin homografts. Thus, infant C3H homografts whose leukocyte populations have been eliminated by X-irradiation or by transient sojourn on an intermediate adult host of the same strain, do not display prolonged survival on CBA Neonatal C3H grafts which precede those from C3H adults are more successful in the induction of unresponsiveness to the latter than neonatal C3H grafts transplanted concomitantly with those of adult origin (9). Thus, proliferation of the emigrating donor leukocytes may contribute to the establishment of tolerance.…”

“…This latter response also occurs in CBA females when newborn grafts of F1 hybrid origin are used. Thus, 77 % of female CBA mice exposed to neonatal skin grafts from (C3H X CBA) F1 mice are unresponsive to these infant homografts and to subsequent grafts from adult C3H animals as well (9). Nevertheless, in view of the sex difference of CBA mice in their reactivity to C3H newborn grafts, male CBA mice were employed primarily in the experiments reported below.…”

“…Even when stronger histoincompatibilities prevail, neonatal transplants exhibit preferential survival. Thus, skin homogrMts from infant C 3 H / H e J mice may persist permanently on CBA/Ss recipients, and may render these hosts tolerant of simultaneous or subsequent adult skin homografts of similar origin (9).…”

“…Preliminary observations indicate that this privilege extended to neonatal skin homografls, including their ability to induce tolerance, may be related to the emigration of donor ]eukocvtes from the graft vasculature (9). The experiments reported below were therefore designed to clarify the role of these "passenger" cells.…”