Studies of the venous homograft.
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Biomedical subjects
Publications and source records attributed to C F Barker.
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Rats of the BN strain, inoculated at birth with (Lewis x BN)F(1) hybrid lymph node cells are not tolerant of Lewis skin grafts but do display high degrees of tolerance of Lewis hearts.
Hamster cheek pouch skin, transplanted to the side of an isogenic host's chest wall, retains its immunologically privileged status as evidenced by the prolonged survival of inlaid homografts of ordinary skin. Various findings sustain the premise that exemption from rejection by otherwise susceptible homografts in both intact pouch tissue and in established pouch skin isografts is due to an impediment in the afferent pathway of the immunologic reflex, i.e., to deficient lymphatic drainage. Although lymphatics were not apparent when dye was injected into pouch skin grafts or into grafts of ordinary skin sustained by them, lymph vessels were readily and consistently revealed by dye injected into intact trunk skin or established isografts of trunk skin. When suspensions of viable lymph node cells from specifically sensitized parental strain donors were injected superficially into either the intact skin or established grafts of normal skin on F(1) hybrid hamsters, a striking hypertrophy of the regional lymph nodes occurred, due to graft-versus-host reactivity. However, similar cell suspensions inoculated into intact pouch tissue or into pouch skin grafts on F(1) hamsters incited no regional lymphadenopathy, indicating the lack of appropriate pathways to the nodes. When skin homografts were inlaid eccentrically into pouch skin isografts, so that they were in contact with host skin at one edge, rejection occurred. Furthermore, rejection of long-established intrapouch skin homografts resulted if the hosts received: (a) small homografts of ordinary skin transplanted to conventional beds; (b) suspensions of donor strain pouch skin epidermal cells, injected intracutaneously; (c) lymph node cells from specifically sensitized donors of the same strain, i.e. adoptive immunization; or, (d) if a portion of the target homograft's perimeter was surgically approximated to body skin. Treatment of normal hamsters with two closely spaced pulses of ALS, although only marginally effective in prolonging the lives of homografts of trunk skin, enabled pouch skin homografts to survive for very long periods. The influence of this brief treatment with immunosuppressant was still demonstrable if challenge of hosts with the weakly immunogenic pouch skin homografts was delayed for 100 days.
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Experiments have been carried out on guinea pigs of two isogenic strains to elucidate the role of afferent lymphatic vessels in the rejection of orthotopic skin homografts. Graft beds were prepared in partially isolated skin flaps with an intact sustaining vascular "umbilical cord" in which a lymphatic connection with the host could be retained or abolished at will. In the absence of demonstrable lymphatic connections between flap and host, intra-flap homografts long outlived similar grafts transplanted to conventional sites in intact skin and, rather than being specifically rejected, died as a consequence of ischemic necrosis of the flap. When lymphatic drainage was retained, intra-flap homografts were rejected in the usual manner. Hosts of long-term intra-flap homografts did not develop sensitivity, as evidenced by the "first set" type rejection of subsequent test grafts, or by the long-term survival of a second skin graft transplanted to a new flap raised on the opposite side of the host's body. Intra-flap skin homografts were rejected if (a) the hosts had been presensitized, (b) they were grafted concomitantly with a skin homograft placed in a conventional site, or inoculated with a suspension of donor lymphoid cells, or (c) if the lymphatic drainage was restored by reimplantation of the hitherto partially isolated flap to an appropriate vascular bed. These findings and others indicate that an intact lymphatic drainage in its bed is essential for an orthotopic skin homograft to sensitize its host. Various experiments were carried out in which intra-flap homografts were used as "indicators" for the acquisition of specific active or adoptive immunity by their hosts. By transplanting skin homografts to conventional beds concomitantly with intra-flap grafts and then excising the former at various intervals, it has been found that a graft must be in residence for a minimum period of 4 days to evoke the development of a detectable level of sensitivity in the host. Furthermore, by replacing either freshly prepared or long-term skin flaps bearing skin homografts in vascular beds on the trunk and determining the subsequent survival times of the homografts, evidence has been obtained suggesting that reestablishment of a functional lymphatic system in a free skin graft may take as long as 9 days. Using intra-flap homografts as indicators of adoptive immunization of the host, we found that as few as 50 x 10(6) isologous peripheral blood leukocytes from a specifically sensitized animal will transfer an effective level of sensitivity. We also found that hyperimmune serum, in relatively large amount, exerts a weak but definite adverse effect upon either freshly or recently transplanted intra-flap grafts.
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