TY - JOUR
T1 - Linked unresponsiveness: Early cytokine gene expression profiles in cardiac allografts following pretreatment of recipients with bone marrow cells expressing donor MHC alloantigen
AU - Spriewald, Bernd M.
AU - Billing, J. Stephen
AU - Ensminger, Stephan M.
AU - Morris, Peter J.
AU - Wood, Kathryn J.
N1 - Funding Information:
This work was supported by The Wellcome Trust, British Heart Foundation and National Heart Research Fund. B.M.S. was supported by the Deutsche Forschungsgemeinschaft (Sp 588-1/1), J.S.B. was a British Heart Foundation Junior Research Fellow and S.M.E. was supported by the ADUMED Stiftung.
PY - 2002
Y1 - 2002
N2 - Linked unresponsiveness operates to induce specific unresponsiveness to fully mismatched vascularized allografts in recipients pretreated with anti-CD4 antibody and syngeneic bone marrow cells expressing a single donor MHC class I alloantigen. The aim of the study was to evaluate early post transplant cytokine expression in allografts where linked unresponsiveness was required for long term graft survival. CBA (H2k) mice were pretreated with CBK (H2k+Kb) bone marrow cells under the cover of anti-CD4 antibody 28 days before transplantation of a CBK or a C57BL/10 (H2b) cardiac allograft. In both cases graft survival was prolonged (MST=100 days). Intragraft expression for interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-10, was determined on day IL-12p40, IL-18, iNOS, transforming growth factor (TGF)-β1 and C-β 1.5, 3, 7 and 14 after transplantation. Whereas rejecting allografts displayed a sharp peak in IFN-γ, IL-2, IL-4 and IL-10 expression, non-rejecting allografts were characterized by an initial TGF-β1 and IFN-γ-production. An increasing IL-4 expression towards day 14 was a unique feature of linked unresponsiveness. All non-rejecting allografts were characterized by an increasing IL-12p40 production towards day 14. In summary, the early cytokine expression pattern in allografts after bone marrow induced operational tolerance is influenced by the quantity of donor alloantigens expressed on the graft as well as on the bone marrow inoculum.
AB - Linked unresponsiveness operates to induce specific unresponsiveness to fully mismatched vascularized allografts in recipients pretreated with anti-CD4 antibody and syngeneic bone marrow cells expressing a single donor MHC class I alloantigen. The aim of the study was to evaluate early post transplant cytokine expression in allografts where linked unresponsiveness was required for long term graft survival. CBA (H2k) mice were pretreated with CBK (H2k+Kb) bone marrow cells under the cover of anti-CD4 antibody 28 days before transplantation of a CBK or a C57BL/10 (H2b) cardiac allograft. In both cases graft survival was prolonged (MST=100 days). Intragraft expression for interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-10, was determined on day IL-12p40, IL-18, iNOS, transforming growth factor (TGF)-β1 and C-β 1.5, 3, 7 and 14 after transplantation. Whereas rejecting allografts displayed a sharp peak in IFN-γ, IL-2, IL-4 and IL-10 expression, non-rejecting allografts were characterized by an initial TGF-β1 and IFN-γ-production. An increasing IL-4 expression towards day 14 was a unique feature of linked unresponsiveness. All non-rejecting allografts were characterized by an increasing IL-12p40 production towards day 14. In summary, the early cytokine expression pattern in allografts after bone marrow induced operational tolerance is influenced by the quantity of donor alloantigens expressed on the graft as well as on the bone marrow inoculum.
UR - http://www.scopus.com/inward/record.url?scp=0036385659&partnerID=8YFLogxK
U2 - 10.1006/cyto.2002.1041
DO - 10.1006/cyto.2002.1041
M3 - Journal articles
C2 - 12200107
AN - SCOPUS:0036385659
SN - 1043-4666
VL - 19
SP - 6
EP - 13
JO - Cytokine
JF - Cytokine
IS - 1
ER -