Suppression of Rat Renal Allograft Rejection by Antigen and Antibody

Stuart, Frank P.; McKearn, Thomas J.; Weiss, Arthur; Fitch, Frank W.

doi:10.1111/j.1600-065x.1980.tb00429.x

Cited by 22 publications

(12 citation statements)

References 83 publications

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“…Moreover, because Lew/BN grafts fare better than similarly sized BN grafts, the relationship between graft size and graft dosage cannot be attributed simply to the availability of more antigen. Indeed, the better survival of Fx hybrid skin grafts on putatively tolerant Lew rats could be related to the ease with which the survival of Lew/BN but not BN kidneys are immunologically enhanced in Lew adults (26).…”

Section: Discussionmentioning

confidence: 99%

Influence of size and gene dosage on the survival of skin allografts on rats rendered tolerant at birth.

Silvers¹,

Collins²,

M³

1983

The Journal of Experimental Medicine

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In most studies on the phenomenon of immunological tolerance as it applies to the cellular antigens responsible for transplantation immunity, neonatal mice or rats are inoculated with suspensions of living, allogeneic cells and, when immunologically mature, challenged with skin allografts of the same genetic origin as the putative tolerance-conferring stimulus. If such grafts are accepted permanently, the animals are judged to be highly or completely tolerant, whereas if the grafts outlive those on untreated recipients but are eventually rejected, the hosts are considered partially or incompletely tolerant. Although there is evidence that exposure to the test graft may sometimes augment the degree of unresponsiveness induced at birth (1), it has generally been assumed that such grafts are indicators of, rather than contributors to, the immunological states of their hosts. We here provide evidence that this assumption is incorrect. Our results indicate that the attributes of the test grafts that putatively tolerant rats are challenged with influence their immune response. Our findings also indicate that the survivals of these grafts are determined by the same factors that operate when only weak histoincompatibilities prevail. Materials and Methods Rats. Major histocompatibility complex (MHC)-incompatible BN/Ss (BN; RTI") andLewis/Ss (Lew; RT11) rats, as well as their F1 hybrids (Lew/BN), were used. The median survival time (MST) of BN (or Lew/BN) skin on adult Lew hosts is ~ 10 d (1).Because there was no difference in the ability of bone marrow cells from reciprocally produced F1 hybrids to induce tolerance of skin, or of skin from these hybrids to survive on tolerant hosts, the results using them have been pooled. There also was no evidence of a sex difference in tolerance susceptibility. Hence, the results with males and females have likewise been pooled.Tolerance Induction. Tolerance was induced by inoculating rats <20 h old intravenously with suspensions of bone marrow cells prepared from adult F1 hybrid animals according to procedures described elsewhere (2).Skin Grafting. Animals were grafted when 2 mo old. Grafting entailed the transfer of fullthickness ventral-trunk skin. The preparation of the grafts, as well as the operative technique, have been described elsewhere (3). First grafts were always transplanted to the right thorax, and second grafts to the left. When animals were grafted simultaneously with two grafts of

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Section: Discussionmentioning

confidence: 99%

Influence of size and gene dosage on the survival of skin allografts on rats rendered tolerant at birth.

Silvers¹,

Collins²,

M³

1983

The Journal of Experimental Medicine

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“…Other potential immunoregulatory events responsible for late graft survival are ill defined. Alterations in the host responses must be responsible as long-standing ailografts do not lose their immunogenicity in time; thus, removal of well-functioning organ grafts and retransplantation of these grafts into new unmodified hosts leads to acute rejection, as also noted in B rats , albeit occasionally in a delayed manner (Stuart et al 1970). Immunologic tolerance, the dilution or elimination of relevant antigenreactive cells from the host, has been difficult to show, as lymphoid cells isolated from recipients of long-surviving grafts can respond to donor type antigens in mixed lymphocyte cultures as well as graft versus host responses when injected into donor strain animals in vivo (Fabre & Morris 1972, Stuart et al i976b).…”

Section: Late Host Unresponstvenessmentioning

confidence: 99%

Mechanisms of Rejection and Prolongation of Vascularized Organ Allografts

Tilney

Kupiec‐Weglinski

Heidecke

et al. 1984

Immunological Reviews

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“…After passive enhancement, grafts survive long after the injected antibody has been metabolized, and in recipients with actively enhanced grafts, the alloantibody titers wane after the first month (3,8). Serum from rats with enhanced grafts will not enhance graft survival in a second host, and attempts to identify antiidiotype or blocking antibodies in the serum have mostly been unsuccessful (2,(9)(10)(11)(12). Attempts to identify the cellular basis of this inhibitory response, which maintains prolonged graft survival, have thus far failed to demonstrate a suppressor cell mechanism.…”

mentioning

confidence: 99%

Mechanisms maintaining enhancement of allografts. I. Demonstration of a specific suppressor cell.

Hall¹

1985

The Journal of Experimental Medicine

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The mechanisms that allow the long-term survival of major histocompatibility complex (MHC)Limmunologically enhanced organ allografts are poorly understood (1-5). In rodents, enhancement can be induced by treatment with either hyperimmune serum at the time of grafting or prior immunization with donor ailoantigen. After a treatment rejection episode, many of these rats develop a state in which the immune system capacity of the host to develop a rejection response is specifically inhibited (1-5). Specific unresponsiveness to donor strain alloantigen in animals with established enhanced grafts is manifested by an inability to reject directly vascularized organ grafts from a second donor strain, but a normal capacity to reject third party grafts (3-6). Also, in rats with enhanced grafts, the rejection of donor strain but not third party skin grafts, is delayed and the length of the delay is inversely related to the time after grafting (7). This suggests that these animals have a specific inhibitory response that matures with time.Although the induction of enhancement is antibody mediated, attempts to demonstrate humoral mediators during the maintenance phase of enhancement have been unsuccessful. After passive enhancement, grafts survive long after the injected antibody has been metabolized, and in recipients with actively enhanced grafts, the alloantibody titers wane after the first month (3,8). Serum from rats with enhanced grafts will not enhance graft survival in a second host, and attempts to identify antiidiotype or blocking antibodies in the serum have mostly been unsuccessful (2, 9-12). Attempts to identify the cellular basis of this inhibitory response, which maintains prolonged graft survival, have thus far failed to demonstrate a suppressor cell mechanism. Hendry et al. (13) demonstrated a specific suppressor cell in thymus and spleen of rats during the induction phase of enhancement, but this effect, which could be transferred to nonimmunosuppressed rats, waned with time and was not demonstrated in the maintenance phase. Fabre and Morris (9) adoptively transferred spleen cells from rats bearing enhanced kidney allografts to normal rats grafted with kidney allografts, but they failed to transfer enhancement. Batchelor et al. (14)

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Suppression of Rat Renal Allograft Rejection by Antigen and Antibody

Cited by 22 publications

References 83 publications

Influence of size and gene dosage on the survival of skin allografts on rats rendered tolerant at birth.

Influence of size and gene dosage on the survival of skin allografts on rats rendered tolerant at birth.

Mechanisms of Rejection and Prolongation of Vascularized Organ Allografts

Mechanisms maintaining enhancement of allografts. I. Demonstration of a specific suppressor cell.

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