Rat Skin Grafts Research Articles

Influence of Langerhans Cells on the Survival of H-Y Incompatible Skin Grafts in Rats

Evidence is presented that Langerhans cells (LCs) play an important role in the rejection of H-Y incompatible skin grafts in BN rats. Not only are small male trunk skin isografts much more likely to be rejected by BN females than similarly sized male foot pad, tail, and ear skin transplants, all of which possess fewer LCs than trunk skin, but the survival of male trunk skin grafts can be prolonged by replacing their LC population with allogeneic female cells.

Biology of Langerhans cells: selective migration of Langerhans cells into allogeneic and xenogeneic grafts on nude mice.

A major question challenging immunobiologists relates to those mechanisms that control the selective movement of cells involved in immune and inflammatory processes at various tissue sites such as the skin. Little is known about those influences that control the selective migration of macrophage-like Langerhans cells (LC) to normal epidermis, where it is uniformly distributed. Mechanistically, this includes the interaction of blood-borne LC precursors with the vascular endothelium of the skin and those factors that control the migration of the LC into the avascular epidermal component of the skin. By using (i) monoclonal antibodies specific for I-region associated Ia antigens found on LC from various inbred strains of animals and (ii) the congenitally athymic (nude) mouse as an immunologically compromised recipient of allografts and selected xenografts, we developed a model system to study the factors that restrict LC migration into the epidermis. Using this model, which excludes the need to lethally x-irradiate graft recipients, we established that: (i) the ingress of LC does not show major histocompatibility complex restriction [LC of the nude host are capable of migrating into the epidermis of allogeneic and certain xenogeneic (rat) skin grafts]; (ii) host LC are incapable of migrating into the epidermis of guinea pig or human skin grafts; (iii) the ingress of host LC into the epidermis of the graft is not accompanied by an overgrowth of the graft by host epidermis; and (iv) LC or LC precursors are capable of dividing in the skin or, alternatively, represent an extremely long-lived cell population. The specificity of this model system provides a powerful tool to help understand many aspects of LC biology. Grafting human skin to the nude mouse not only provides a biologic support system for the graft but also is, by design, a system that is devoid of contaminating circulating precursor cell types. Manipulation of the experimental conditions is quite easy and provides a highly specific means to investigate many parameters of LC function.

同種皮膚移植における皮膚上皮細胞に対する免疫能の変動

同種皮膚移植における皮膚上皮細胞に対する免疫能の変動

Inhibitory effects of 5-azapyrimidine nucleosides on cellular immunity

The effect of 5-azacytidine (5-AzCR) and 5-aza-deoxycytidine (5-AzCdR) on the survival of skin grafts in mice and rats, the action of these drugs on regional GVH reaction, as well as the formation of haemopoietic colonies (CFU-S) in the spleen were studied. Both drugs prolonged the life span of skin grafts when administered 24 hr before transplantation, or on the 4th post-transplantation day. However, they were little effective when injected 24 hr after skin grafting, or after induction of the regional GVHR. Following intraperitoneal administration, they inhibited CFU-S formation. Two-hour incubation in vitro of cells with 5-AzCR significantly reduced their GVH reactivity and capacity to form CFU-S; 5-AzCdR under the same conditions was ineffective.

Studies on the behavior of H-Y incompatible skin grafts in rats.

Studies on the behavior of H-Y incompatible skin grafts in rats indicate that 1) there is considerable variation in the ability of females of different strains to reject male skin isografts; 2) small, male trunk skin isografts are more likely to be rejected than similarly sized ear or tail skin grafts; 3) other factors besides the MHC plan an important role in determining the ability of females to reject male skin isografts; 4) the ability of adult male skin grafts to induce unresponsiveness to H-Y depends upon their size (large grafts are more effective than small) and the genotype of the host; 5) even in those strains in which females usually accept small, male trunk skin isografts, such grafts are acutely rejected by sensitized females; and 6) the total amount of H-Y incompatible trunk skin the host is exposed to, rather than the size of each graft, determines their fate.

Blood flow, histamine content and histidine decarboxylase (HDC) activity in rat skin grafts and their modification by cyclosporin-A (CSA)

Blood flow, histamine content and histidine decarboxylase (HDC) activity in rat skin grafts and their modification by cyclosporin-A (CSA)

THE BEHAVIOR OF H-Y-ENCOMPATIBLE NEONATAL SKIN GRAFTS IN RATS1

It has been well documented that virgin female rats previously systemically sensitized against H-Y antigen almost invariably reject male skin isografts of adult origin. However, when the donor is a neonatal animal, these H-Y-incompatible grafts are often permanently accepted. Furthermore, such neonatal male skin grafts are frequently able to induce a state of unresponsiveness to subsequent grafts of adult male skin. This ability to induce tolerance is evidently dependent upon the persistence of the neonatal skin graft as it does not occur if the neonatal graft is rejected. Thus, the behavior of H-Y-incompatible neonatal skin grafts in rats parallels their behavior in mice.

Acute Destruction of Rat Skin Grafts by Alloantisera

Rat skin transplanted to mice or to allogeneic rats can be acutely and severely damaged by injecting the graft recipients with alloimmune serum of appropriate specificity. This susceptibility of rat skin to alloantisera has been obscured in previous studies by the fact that the extent of serum-mediated damage that occurs is decisively influenced by the interval of time between placement of the grafts and the injection of antiserum. Grafts are resistant to damage during the 1st week after transplantation; they rapidly develop sensitivity during the 2nd week, reaching a peak at 14 to 16 days; and during the next few weeks the sensitivity is lost. Grafts surviving beyond 35 to 40 days become totally resistant to antisera. LBNF1 GRAFTS Are more resistant than Le or BN grafts to BN anti-Le serum or Le anti-BN serum, respectively. However, combinations of the two sera can act synergistically to destroy LBN skin that has been grafted to immunosuppressed mice. This form of serum-mediated tissue damage is thought not to play a significant role in skin graft rejection in the usual circumstances of transplantation since cell mediated immunity is well developed before the acquisition by the grafts of sensitivity to humoral agents. Furthermore, antisera from animals that have rejected a single graft have little or no destructive potential, and hyperimmune animals reject skin very shortly after grafting, often before the grafts have become vascularized and hence before they are sensitive to antiserum.

Skin graft survival on avascular defects.

Full-thickness skin grafts placed on bare rabbit ear cartilage were revascularized, whereas split-skin grafts on the same kinds of areas failed. The contrast is most likely due to differences in the skin graft thickness and the vascular patterns in the grafts. Full-thickness rat skin grafts placed over the same sized underlying silicone sheet implants did not survive. When the graft was made 3 mm larger on all sides than the implant, all or a portion of the graft over the implant survived. Quantitation of the area of graft survival is presented. Prepared grafts (replaced on their donor areas for 48 hours) on prepared beds and fresh grafts on prepared beds had slightly larger areas of graft surviving over an avascular defect. On the basis of this investigation, we suggest that a full-thickness skin graft placed on a prepared peripheral bed may make possible the greatest area of bridging over an avascular defect.

The effect of nondefatting for frozen tissue preservation of rat skin grafts

The effect of nondefatting for frozen tissue preservation of rat skin grafts

Induction of tolerance in rats by treatment with antithymocyte serum and adult skin homografts

ACI rats bearing healthy DA skin homografts > 150 days after completion of a 35-day course of antithymocyte serum given at the time of grafting, accepted another DA skin graft for > 150 days. These animals promptly rejected third-party skin and transfer of the long-surviving homografts to new ACI hosts resulted in acute rejection, ruling out adaptation. Use of serum from hosts of long-accepted skin did not enhance survival of donor strain skin grafts in rats of the recipient strain. Specific unresponsiveness (tolerance) seems to have been achieved as the result of immunosuppression and adult skin as the only source of antigen.

The effect of combined immunosuppressive agents and cell-free antigen on xenograft survival.

SUMMARY Mice receiving rat skin grafts were treated with the immunosuppressive agents procarbazine, rabbit antimouse lymphocyte serum (RAMLS), and acriflavine, either alone or in combination with each other. Although the three drugs had different toxicities, overimmunosuppression and high mortality in the absence of drug-specific toxicity resulted when the agents were used together. In an attempt to avoid this high mortality, the three drugs were administered in varying dosages and combined with cell free antigen (CFA). The results indicate that CFA leads to more prolonged graft survival when combined with varying dosages of the three drugs. The presence of acriflavine. a known suppressant of antibody formation, appears necessary for CFA to be an effective adjuvant

Significance of serum N-acetyl-beta-D-glucosaminidase in tissue rejection.

By determining the release of various enzymes in serum, it was possible to distinguish between the ischemic damage resulting from the surgical procedure and by the rejection process in canine renal transplantation. The enzyme release during rejection was preceded by an increase of the lysosomal N-acetyl-B-glucosaminidase activity. Serum-N-acetyl-β-glucosaminidase activity was also elevated during the rejection of skin grafts in rats. The elevation of this enzyme was suppressed by intraperitoneally injected Imuran. The serum enzyme activity did not increase secondarily in skin autografts. Based upon the observation that normal guinea pig serum contains N-acetyl-β-glucosaminidase activities tenfold higher than in other animals, the properties of this enzyme in serum were investigated in diluted guinea pig serum and inhibition studies were performed.

Tolerance of rat skin grafts in adult mice

Abstract Adult CBA mice may be made tolerant of August rat tail skin grafts by short intensive treatments with antilymphocyte serum followed by massive (∼100 × 106 cells) injections of August rat lymphoid cells. Prolonged tolerance can be achieved only in thymectomized mice, and is accompanied by lymphoid cell chimerism and the manufacture of rat protein. The rat lymphoid cell donors must be treated beforehand with antirat ALS to avoid complications associated with graft versus host reactions. Rejection of rat skin grafts is accompanied by the formation of high titres of antirat hemolysins and lymphocytotoxins, but in “tolerant” mice the rat skin survives in the continual presence of antirat antibodies. Under certain circumstances, however, passive transfusion of high titre mouse antirat serum can precipitate the breakdown of rat skin grafts. It is doubtful if this represents the primary mechanism of rejection. The reaction of normal mice against rat skin is essentially an intensified allograft reaction; it is at all events wholly immunological in character.

Tolerance of rat skin grafts in adult mice.

Adult CBA mice may be made tolerant of August rat tail skin grafts by short intensive treatments with antilymphocyte serum followed by massive ( approximately 100 x 10(6) cells) injections of August rat lymphoid cells. Prolonged tolerance can be achieved only in thymectomized mice, and is accompanied by lymphoid cell chimerism and the manufacture of rat protein. The rat lymphoid cell donors must be treated beforehand with antirat ALS to avoid complications associated with graft versus host reactions. Rejection of rat skin grafts is accompanied by the formation of high titres of antirat hemolysins and lymphocytotoxins, but in "tolerant" mice the rat skin survives in the continual presence of antirat antibodies. Under certain circumstances, however, passive transfusion of high titre mouse antirat serum can precipitate the breakdown of rat skin grafts. It is doubtful if this represents the primary mechanism of rejection. The reaction of normal mice against rat skin is essentially an intensified allograft reaction; it is at all events wholly immunological in character.

Skin grafts in Donryu rats with and without acquired resistance to Yoshida sarcoma and ascites hepatomas.

Skin grafts in Donryu rats with and without acquired resistance to Yoshida sarcoma and ascites hepatomas.

43. Effects of prolonged hypothermia on skin grafts in rats: Kimiyoshi Tsuji and William W. Shingleton (Department of Surgery, Duke University, Durham, North Carolina)

43. Effects of prolonged hypothermia on skin grafts in rats: Kimiyoshi Tsuji and William W. Shingleton (Department of Surgery, Duke University, Durham, North Carolina)

Differential Response to Allogenic and Xenogenic Skin Grafts by Sublethally Irradiated (670 RAD) and Nonirradiated Mice Sensitized by Various Means

Summary Data are presented demonstrating in sublethally x-irradiated (670 rad) mice the differential radiosensitivity of the first and second-set responses to allogenic (H-2 difference) and xenogenic (rat) skin grafts. The second-set response is more radioresistant than is the first-set response; the second-set response to a xenogenic skin graft is more radioresistant than is that to an allogenic graft; the converse is true with regard to the first set response. The “homograft sensitivity” induced with xenogenic or allogenic dissociated skin or spleen cells (with the methods used) appears to be “inferior” to or unlike that induced with skin grafts. Sensitization with xenogenic dissociated cells resulted in a more vigorous response (i.e., shorter rejection time) to subsequent appropriate grafts in both nonirradiated and sublethally irradiated mice than did sensitization with comparable allogenic tissues. Allogenic skin grafts survived significantly longer on sublethally irradiated mice, presensitized with allogenic dissociated spleen cells than they did on the appropriate controls. By contrast, presensitization with allogenic dissociated skin cells had essentially no effect on allogenic graft survival in sublethally irradiated mice. Nonirradiated and sublethally irradiated (670 rad) mice previously sensitized with rat skin grafts rejected subsequent first-set allogenic grafts significantly sooner than did their appropriate controls. This effect was not seen when the mice had been previously sensitized with dissociated rat skin or spleen cells. Neither the initial method of sensitization nor sublethal irradiation influenced the sensitization induced by subsequent skin grafts. Certain observations made during the accelerated rejection of allogenic and particularly of xenogenic skin grafts suggested either the presence of a nonspecific agent capable of disrupting the capillary bed at the graft sites or the deficiency of a factor essential to the maintenance of capillary wall integrity.

DIFFERENTIAL RADIOSENSITIVITY OF FIRST AND SECOND-SET RESPONSES TO ALLOGENEIC AND XENOGENEIC SKIN GRAFTS IN LETHALLY IRRADIATED MICE.

The second-set response of mice presensitized by means of allogeneic (H-2 difference) or xenogeneic (rat) skin grafts is more resistant to a lethal dose of X-radiation (870 rad) than is the first-set response. The second-set response to a xenogeneic skin graft is more radioresistant than is the second-set response to an allogeneic graft. The first-set response to an allogeneic skin graft appears to be more radioresistant than is the first-set response to a xenogeneic graft. Presensitization by means of rat skin grafts accelerated the primary response to an allogeneic skin graft in non-irradiated mice. The converse was not true. The theoretical implications of these observations are briefly discussed. The data are interpreted as clear evidence of the heterogeneity of the mammalian immune system.

Differential response to allogenic and xenogenic skin grafts by sublethally irradiated (670 rad) and non-irradiated mice sensitized by various means.

1. 1. Data are presented demonstrating in sublethally x-irradiated (670 rad) mice the differential radiosensitivity of the first and second-set responses to allogenic (H-2 difference) and xenogenic (rat) skin grafts. The second-set response is more radioresistant than is the first-set response; the second-set response to a xenogenic skin graft is more radioresistant than is that to an allogenic graft; the converse is true with regard to the first set response. 2. 2. The “homograft sensitivity” induced with xenogenic or allogenic dissociated skin or spleen cells (with the methods used) appears to be “inferior” to or unlike that induced with skin grafts. Sensitization with xenogenic dissociated cells resulted in a more vigorous response ( i.e. , shorter rejection time) to subsequent appropriate grafts in both nonirradiated and sublethally irradiated mice than did sensitization with comparable allogenic tissues. 3. 3. Allogenic skin grafts survived significantly longer on sublethally irradiated mice, presensitized with allogenic dissociated spleen cells than they did on the appropriate controls. By contrast, presensitization with allogenic dissociated skin cells had essentially no effect on allogenic graft survival in sublethally irradiated mice. 4. 4. Nonirradiated and sublethally irradiated (670 rad) mice previously sensitized with rat skin grafts rejected subsequent first-set allogenic grafts significantly sooner than did their appropriate controls. This effect was not seen when the mice had been previously sensitized with dissociated rat skin or spleen cells. 5. 5. Neither the initial method of sensitization nor sublethal irradiation influenced the sensitization induced by subsequent skin grafts. 6. 6. Certain observations made during the accelerated rejection of allogenic and particularly of xenogenic skin grafts suggested either the presence of a nonspecific agent capable of disrupting the capillary bed at the graft sites or the deficiency of a factor essential to the maintenance of capillary wall integrity.