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108 Abstracts rejection, nevertheless, a subset of patients with concomitant renal and hepatic dysfunction (Group 1), with historically poor prognosis, appeared to benefit from monoclonal therapy, as demonstrated by normalization of their survival curves. INDEFINITE SURVIVAL OF ENDOCRINE ALLOGRAFTS WITH NO POSTOPERATIVE IMMUNOSUPPRESSION. H. Gebel, Y. Umeki, S. Economou, and A. Bloom; Rush-Medical Center, Chicago, IL Previous studies demonstrate that endocrine allografts in mice survive indefinitely if Ia + dendritic cells are eliminated before transplant. In rats, however, depletion of Ia + cells alone does not dramatically extend graft survival. In this study, we demonstrate that elimination of Ia + cells in rat parathyroid glands before trans- plant extends allograft survival indefinitely when cyclosporine (CYS) is admin- istered to the recipients preoperatively. Glands from RT TM donors were either: (1) cultured for 1 week at 37°C and treated with anti-Ia and complement or (2) cultured (only) for 1 week at 37°C. Glands were transplanted, intramuscularly, into parathyroidectomized, RT1 u controls (nonimmunosuppressed) or recipients given 30 mg/kg/day of CYS for the 3 days prior to transplant. Controls (n = 7) transplanted with cultured parathyroid glands not treated with anti-Ia had a mean graft survival of 17.5 days; recipients treated preoperatively with CYS (n = 7) had a mean survival of 80.5 days. When Ia-depleted parathyroid glands were transplanted into cyclosporine-treated recipients (n = 9), three animals rejected their grafts within 25 days; the remaining six animals (67%) continue to have functional grafts 1 yr post-transplant. Graft excision at this time resulted in hypocalcemia, and histologic examination of the excised grafts demonstrated intact parathyroid tissue with no lymphocytic infiltration. Similar studies were initiated for islet cell transplants. Diabetic recipients were given CYS for 3 days and transplanted with 1500 allogeneic islets beneath the renal capsule. Controls (n = 6) rejected the islets within 7 days, while 6/6 CYS-treated recipients are euglycemic for >50 days. We believe that techniques to reduce endocrine al- lograft immunogenicity, especially when coupled to pretransplant cyclosporine therapy, may eventually replace lifetime immunosuppression of human transplant recipients. (Supported, in part, by NIH PHS grant #AM35545.) REACTIVITY PATTERNS OF ALLOREACTIVE LYMPHOCYTES PROPAGATED FROM HEART BIOPSIES AND PERIPHERAL BLOOD FROM HEART TRANSPLANT RECIPIENTS. Christina Kaufman, Adriana Zeevi, John Fung, Tony Zerbe, Bartley Griffith, Robert Kormos, Alfredo Trento, Robert Hardesty, and Rene Duquesnoy; Division of Clinical Immunpathology and Department of Surgery, University of Pittsburgh and Central Blood Bank, Pittsburgh, PA We have previously shown that activated lymphocytes propagated from heart biopsies (HB) from cardiac transplant recipients, exhibit donor-specific alloreac- tive responses. Biopsies, obtained 4-6 weeks post-transplant, generally yielded lymphocytes recognizing primarily class I antigens or a mixture of class I and II antigens, whereas later biopsies grew primarily class II specific PLT cells. These results indicate a selectivity in the types of cells infiltrating the cardiac allograft. Frequently, the PLT specificity of HB lymphocytes is restricted towards one or two donor HLA antigens. This selectivity of lymphocyte infiltration in HB could be a direct result of a limited cellular response to donor HLA antigens or it could be due to the restricted allorecognition of endothelium which is the primary target of alloreactive T cells during the initiation of allograft rejection. To gain

Indefinite survival of endocrine allografts with no postoperative immunosuppression

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108 Abstracts

rejection, nevertheless, a subset of patients with concomitant renal and hepatic dysfunction (Group 1), with historically poor prognosis, appeared to benefit from monoclonal therapy, as demonstrated by normalization of their survival curves.

INDEFINITE SURVIVAL OF ENDOCRINE ALLOGRAFTS WITH NO POSTOPERATIVE IMMUNOSUPPRESSION. H. Gebel, Y. Umeki, S. Economou, and A. Bloom; Rush-Medical Center, Chicago, IL

Previous studies demonstrate that endocrine allografts in mice survive indefinitely if Ia + dendritic cells are eliminated before transplant. In rats, however, depletion of Ia + cells alone does not dramatically extend graft survival. In this study, we demonstrate that elimination of Ia + cells in rat parathyroid glands before trans- plant extends allograft survival indefinitely when cyclosporine (CYS) is admin- istered to the recipients preoperatively. Glands from RT TM donors were either: (1) cultured for 1 week at 37°C and treated with anti-Ia and complement or (2) cultured (only) for 1 week at 37°C. Glands were transplanted, intramuscularly, into parathyroidectomized, RT1 u controls (nonimmunosuppressed) or recipients given 30 mg/kg/day of CYS for the 3 days prior to transplant. Controls (n = 7) transplanted with cultured parathyroid glands not treated with anti-Ia had a mean graft survival of 17.5 days; recipients treated preoperatively with CYS (n = 7) had a mean survival of 80.5 days. When Ia-depleted parathyroid glands were transplanted into cyclosporine-treated recipients (n = 9), three animals rejected their grafts within 25 days; the remaining six animals (67%) continue to have functional grafts 1 yr post-transplant. Graft excision at this time resulted in hypocalcemia, and histologic examination of the excised grafts demonstrated intact parathyroid tissue with no lymphocytic infiltration. Similar studies were initiated for islet cell transplants. Diabetic recipients were given CYS for 3 days and transplanted with 1500 allogeneic islets beneath the renal capsule. Controls (n = 6) rejected the islets within 7 days, while 6/6 CYS-treated recipients are euglycemic for >50 days. We believe that techniques to reduce endocrine al- lograft immunogenicity, especially when coupled to pretransplant cyclosporine therapy, may eventually replace lifetime immunosuppression of human transplant recipients. (Supported, in part, by N I H PHS grant #AM35545.)

REACTIVITY PATTERNS OF ALLOREACTIVE LYMPHOCYTES PROPAGATED FROM HEART BIOPSIES AND PERIPHERAL BLOOD FROM HEART TRANSPLANT RECIPIENTS. Christina Kaufman, Adriana Zeevi, John Fung, Tony Zerbe, Bartley Griffith, Robert Kormos, Alfredo Trento, Robert Hardesty, and Rene Duquesnoy; Division of Clinical Immunpathology and Department of Surgery, University of Pittsburgh and Central Blood Bank, Pittsburgh, PA

We have previously shown that activated lymphocytes propagated from heart biopsies (HB) from cardiac transplant recipients, exhibit donor-specific alloreac- tive responses. Biopsies, obtained 4 -6 weeks post-transplant, generally yielded lymphocytes recognizing primarily class I antigens or a mixture of class I and II antigens, whereas later biopsies grew primarily class II specific PLT cells. These results indicate a selectivity in the types of cells infiltrating the cardiac allograft. Frequently, the PLT specificity of HB lymphocytes is restricted towards one or two donor HLA antigens. This selectivity of lymphocyte infiltration in HB could be a direct result of a limited cellular response to donor HLA antigens or it could be due to the restricted allorecognition of endothelium which is the primary target of alloreactive T cells during the initiation of allograft rejection. To gain