Extensive Prolongation of Rat Renal Allograft Survival Following Donor or Nonspecific Transfusions and Concomitant Immunosuppressant1

Martin, Donald C.; Hewitt, Charles W.; Black, Kirby S.; Dowdy, Steven F.; Quintero, Carolyn S.; Reyes, Marcelo

doi:10.1097/00007890-198743060-00003

Cited by 4 publications

(2 citation statements)

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“…Recipients underwent bilateral nephrectomy [8]. Grafting involved anastomosis of the donor renal artery to the recipient abdominal aorta, the donor renal vein to the recipient inferior vena cava and a donor bladder patch to the recipient bladder.…”

Section: Methodsmentioning

confidence: 99%

Mechanisms of unresponsiveness associated with pretransplant blood transfusion - cyclosporine-induced mixed lymphocyte chimerism

et al. 1994

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Multiple pretransplant blood transfusions while under limited daily cyclosporine cover (PTBT-CsA) induce extensive rat renal allograft survival and antigen-specific non-responsiveness. The underlying mechanisms of this extensive allograft survival are not yet fully understood. We hypothesized that one of the potential contributing mechanisms to tolerance induction in PTBT-CsA-treated kidney recipients is the development of stable mixed chimerism, putatively due to the proliferation of stem cells capable of haematopoiesis in the transfused blood. BN rats served as whole blood and kidney donors. LEW rats served as recipients of the PTBT-CsA protocol and BN kidney transplants. Three weekly transfusions were given under concomitant limited CsA cover. Following these multiple primary sensitizations, antigen-specific splenic cellular responsiveness in vivo was normal in comparison with naive animals. However, these experimental splenocytes were non-specifically suppressed against third-party allodeterminants. At 100 days post-transplantation (T100) following tolerance induction to kidney allografts (secondary challenge), in vivo adoptive transfer experiments demonstrated the existence of potent splenic suppressor cells. In vitro suppressor cell assays confirmed that these cells were non-specific suppressor cells. However, following chimerism stabilization at T130, splenic antigen-specific suppressor cells became exclusively expressed in the tolerant animals, replacing the non-specific suppressor cells. At this time, splenic microchimerism was at peak levels and remained stable from T100 to T130. In conclusion, these findings demonstrate that sequential mechanisms of suppressor cell network expression are induced within a chimeric environment by blood-CsA immune modulation. Stable mixed lymphocyte chimerism and related immunomodulatory mechanisms may, therefore, play an important tolerogenic role in blood-CsA-induced non-responsiveness and in the beneficial effect of blood transfusion.

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Section: Methodsmentioning

confidence: 99%

Mechanisms of unresponsiveness associated with pretransplant blood transfusion - cyclosporine-induced mixed lymphocyte chimerism

et al. 1994

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“…The transplant recipients consisted of the following four groups: rats ( n = 4) receiving no immunosuppression; rats ( n = 5 ) receiving pretransplantation cyclosporin ( 5 mg/kg/day X 23 days with discontinuation 5 days prior to transplantation); rats ( n = 6) receiving pretransplantation multiple donor-specific blood transfusions (three separate 1-ml transfusions of BN blood each week for 3 weeks prior to transplantation) and cyclosporin ( 5 mg/kg/day X 23 days as above); and rats ( n = 6) receiving donor-nonspecific (three separate 1 -ml transfusions of DA, BUF, and WKY blood each week for 3 weeks prior to transplantation) blood transfusions and cyclosporin ( 5 mg/kg/day X 23 days as above). The survival times and blood urea nitrogen levels as well as other information regarding these groups has been previously reported ( 15).…”

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The Development of Humoral Immunity to Tissue-Specific Tubular Basement Membrane Alloantigens after Renal Transplantation across the Major Histocompatibility Barrier in Rats Immunomodulated with Blood Transfusions and Cyclosporin

Ulich

Hewitt

et al. 1988

Experimental Biology and Medicine

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The development of a humoral immune response to the tubular basement membrane (TBM) alloantigen of Brown-Norway (BN) rat kidneys was studied after transplantation of BN rat kidneys into bilaterally nephrectomized Lewis (LEW) rats. The LEW rat recipients consisted of four groups receiving no form of immunosuppression, pretransplantation cyclosporin alone, or pretransplantation donor-specific or donor-nonspecific transfusions combined with cyclosporin. The latter two regimens induce indefinite allograft survival in the majority of recipients. Circulating antibody to collagenase-solubilized BN rat renal basement membrane (CS-BN-RBM) was present in all four groups of transplant recipients within 1 week after transplantation, and no significant differences in antibody levels were noted between rats receiving no immunosuppression (survival of 1-2 weeks) and the groups of rats who received various immunosuppressive regimens and survived longer. Circulating antibody to BN-CS-RBM continued to increase in quantity in the cyclosporin-treated group until the time of death (2-10 weeks post-transplantation). In the much longer lived combined transfusion and cyclosporin-treated groups, circulating antibody to BN-CS-RBM generally attained a maximum at Downloaded from Norway rats by ( 1 5s)-15-methyl prostaglandin El :Analysis of the effect of prostaglandin El on the induction of the humoral immune response and the elicitation of humorally-meidated inflammation.

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The Effect of Ureteric Stenting on the Function and Morphology of Long‐term Rat Renal Allografts

Jablonski

Baxter

Howden

et al. 1995

Australian and New Zealand Journal of Surgery

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In the development of a reliable model for chronic rejection in rat renal allografts. the effect of modifying the ureteric anastomosis was tested. Rats. tolerized by pretreatment with two donor blood transfusions under Cyclosporin A. received renal allografts with either sewn or stented ureter. Control groups received isografts or underwent uninephrectomy with insertion of ureteric stents. For the first 6 days after transplantation, serum creatinine and urea values were lower in allograft recipients with stented ureters than in the group with sewn ureters. The method of ureteric anastomosis did not affect the long‐term incidence of abnormal function. Allograft morphology was extremely variable from minor to extensive tubular atrophy. interstitial tibrosis. glomerular hypertrophy, focal and segmental glomerulosclerosis as well as vascular changes. Glomerulosclerosis was absent in controls and increased with time in the allografts. Two hundred days after transplantation all allograft recipients with sewn ureters exhibited some glomerulosclerosis, in half of these kidneys more than 25% of glomeruli were affected. Only 33% recipients of allografts with stented ureters exhibited some glomerulosclerosis and less than 20% of glomeruli were affected. The stented ureteric anastomosis provides a reliable method, a reduction of the technical failure rate, a reduction of the incidence of hydronephrosis, allows more accurate assessment of early renal function and may be of importance in reducing the occurrence and prevalence of glomerulosclerosis in the long‐term allografts.

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Extensive Prolongation of Rat Renal Allograft Survival Following Donor or Nonspecific Transfusions and Concomitant Immunosuppressant1

Cited by 4 publications

References 0 publications

Mechanisms of unresponsiveness associated with pretransplant blood transfusion - cyclosporine-induced mixed lymphocyte chimerism

Mechanisms of unresponsiveness associated with pretransplant blood transfusion - cyclosporine-induced mixed lymphocyte chimerism

The Development of Humoral Immunity to Tissue-Specific Tubular Basement Membrane Alloantigens after Renal Transplantation across the Major Histocompatibility Barrier in Rats Immunomodulated with Blood Transfusions and Cyclosporin

The Effect of Ureteric Stenting on the Function and Morphology of Long‐term Rat Renal Allografts

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