Mechanisms of immunologic unresponsiveness induced by ultraviolet-irradiated donor-specific blood transfusions and peritransplant cyclosporine
Journal Article
·
· Transplantation; (United States)
Recipient pretreatment with UV-B irradiated donor-specific blood transfusions (UV-DST) combined with peritransplant cyclosporine on days 0, +1, and +2 leads to permanent cardiac allograft survival in the ACI-to-Lewis rat strain combination. This study investigates the mechanisms of immunologic unresponsiveness induced by UV-DST and CsA by examining several in vitro and in vivo parameters in long-term cardiac allograft recipients. The results of the in vitro studies demonstrate that thoracic duct lymphocytes (TDL) of treated and allografted Lewis rats respond less in a mixed lymphocyte reaction to donor splenic lymphocytes (SpL) by 69%, 75%, and 73% (P less than 0.001) at 30, 50, and 100 days after transplantation, respectively, compared with controls, while the response to a third-party (W/F) SpL is unimpaired. In coculture experiments, the TDL from treated recipients specifically suppressed the response of unmodified Lewis TDL to ACI SpL by 59% and 40% (P less than 0.01) at 30 and 50 days after transplantation, respectively, while responses to W/F SpL were suppressed by only 3-6%. The sera obtained from ungrafted rats transfused with UV-DST suppressed the MLR between unmodified Lewis TDL and ACI SpL by 31% (P less than 0.05) while the sera from UV-DST and CsA-treated and allografted rats specifically suppressed the MLR by 75%, 80% (P less than 0.001) and 37% (P less than 0.01) at 10, 30, and 50 days after transplantation, respectively. In vivo adoptive transfer of 10(4) donor-type dendritic cells (DC) into recipients of beating cardiac allografts at 40 or 60 days after transplantation led to rapid and acute allograft rejection, while the adoptive transfer of 10(8) unseparated SpL obtained at 50 days after transplantation from treated Lewis recipients to syngeneic naive hosts led to a modest but significant prolongation of ACI test cardiac allografts.
- Research Organization:
- Columbia Univ. College of Physicians and Surgeons, New York, NY (USA)
- OSTI ID:
- 6745199
- Journal Information:
- Transplantation; (United States), Journal Name: Transplantation; (United States) Vol. 46:3; ISSN TRPLA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARDIOVASCULAR SYSTEM
CONNECTIVE TISSUE CELLS
DRUGS
ELECTROMAGNETIC RADIATION
GRAFT-HOST REACTION
HEART
IMMUNITY
IMMUNOSUPPRESSION
IMMUNOSUPPRESSIVE DRUGS
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
ORGANS
RADIATIONS
RADIOINDUCTION
RATS
RODENTS
SOMATIC CELLS
SPLEEN
THERAPY
TRANSFUSIONS
TRANSPLANTS
ULTRAVIOLET RADIATION
VERTEBRATES
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
ANIMALS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY
BODY FLUIDS
CARDIOVASCULAR SYSTEM
CONNECTIVE TISSUE CELLS
DRUGS
ELECTROMAGNETIC RADIATION
GRAFT-HOST REACTION
HEART
IMMUNITY
IMMUNOSUPPRESSION
IMMUNOSUPPRESSIVE DRUGS
LEUKOCYTES
LYMPHOCYTES
MAMMALS
MATERIALS
ORGANS
RADIATIONS
RADIOINDUCTION
RATS
RODENTS
SOMATIC CELLS
SPLEEN
THERAPY
TRANSFUSIONS
TRANSPLANTS
ULTRAVIOLET RADIATION
VERTEBRATES