Analysis of functional renal allograft tolerance with single-dose rapamycin based induction immunosuppression

William C. Goggins, Robert A. Fisher, Jeffery Dattilo, Dennis S. Cohen, John W. Tawes, Mary Peace M. Dattilo, George F. Babcock, Susan E. Frede, Paul E. Wakely, Marc P. Posner

    Research output: Contribution to journalArticle

    14 Citations (Scopus)

    Abstract

    The induction of transplantation tolerance is one of the primary goals following solid organ transplantation. The combination of a single dose of rapamycin (RAPA) with a short course of cyclosporine (CsA) has been shown to induce transplantation tolerance in the nonfunctional rat heterotopic cardiac transplant model. The purpose of this study was to assess this effective induction protocol in a functional renal transplant model. Male ACI (RTla) and Lewis (RTl1) rats were used as donor and recipients respectively. Allografts received a single RAPA dose of (1.5 mg/kg) combined with CsA (10 mg/kg) 12-14 hr prior to transplantation. CsA (5 mg/kg) was given daily on days +1+7. Untreated Lewis to Lewis isografts served as histological controls. Chimerism, assessed in recipient skin, and intragraft interleukin (IL) 10 expression was determined utilizing PCR and RT-PCR techniques respectively. Treated animals and isografts were sacrificed 120-130 days posttransplant for functional and histological evaluation. Allografts (n=9) were functionally tolerant with serum creatinine (0.77±0.1 vs. 0.88±0.1; P=0.275), blood urea nitrogen (37.6±4.6 vs. 23.3±1.9; P=0.123), and 24 hr protein excretion (27.0±4.4 vs. 17.9±5.2; P=0.131) similar to single kidney ACI controls. Histologically, 45% (4/9) allografts were indistinguishable from isografts with no evidence of rejection, and were considered immunologically tolerant. Donor/recipient chimerism was not detected. All immunologically tolerant allografts had evidence of intragraft IL-10 expression. Rejecting allografts and isografts did not express intragraft IL- 10. This study confirms the efficacy of pre-engraftment single-dose RAPA combined with CsA in inducing true immunologic tolerance in this stringent functional renal transplant model. The expression of intragraft IL-10 in tolerant recipients suggests a Th-2 shift as the mechanism of tolerance in this model.

    Original languageEnglish (US)
    Pages (from-to)310-314
    Number of pages5
    JournalTransplantation
    Volume63
    Issue number2
    DOIs
    StatePublished - Jan 27 1997

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    Transplantation Tolerance
    Isografts
    Sirolimus
    Immunosuppression
    Allografts
    Interleukin-10
    Kidney
    Chimerism
    Transplants
    Polymerase Chain Reaction
    Blood Urea Nitrogen
    Organ Transplantation
    Cyclosporine
    Creatinine
    Transplantation
    Skin
    Serum
    Proteins

    All Science Journal Classification (ASJC) codes

    • Transplantation

    Cite this

    Goggins, W. C., Fisher, R. A., Dattilo, J., Cohen, D. S., Tawes, J. W., Dattilo, M. P. M., ... Posner, M. P. (1997). Analysis of functional renal allograft tolerance with single-dose rapamycin based induction immunosuppression. Transplantation, 63(2), 310-314. https://doi.org/10.1097/00007890-199701270-00023

    Analysis of functional renal allograft tolerance with single-dose rapamycin based induction immunosuppression. / Goggins, William C.; Fisher, Robert A.; Dattilo, Jeffery; Cohen, Dennis S.; Tawes, John W.; Dattilo, Mary Peace M.; Babcock, George F.; Frede, Susan E.; Wakely, Paul E.; Posner, Marc P.

    In: Transplantation, Vol. 63, No. 2, 27.01.1997, p. 310-314.

    Research output: Contribution to journalArticle

    Goggins, WC, Fisher, RA, Dattilo, J, Cohen, DS, Tawes, JW, Dattilo, MPM, Babcock, GF, Frede, SE, Wakely, PE & Posner, MP 1997, 'Analysis of functional renal allograft tolerance with single-dose rapamycin based induction immunosuppression', Transplantation, vol. 63, no. 2, pp. 310-314. https://doi.org/10.1097/00007890-199701270-00023
    Goggins, William C. ; Fisher, Robert A. ; Dattilo, Jeffery ; Cohen, Dennis S. ; Tawes, John W. ; Dattilo, Mary Peace M. ; Babcock, George F. ; Frede, Susan E. ; Wakely, Paul E. ; Posner, Marc P. / Analysis of functional renal allograft tolerance with single-dose rapamycin based induction immunosuppression. In: Transplantation. 1997 ; Vol. 63, No. 2. pp. 310-314.
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