TY - JOUR
T1 - Increased expression of transforming growth factor-β and eosinophil infiltration is associated with the development of transplant arteriosclerosis in long-term surviving cardiac allografts
AU - Spriewald, Bernd M.
AU - Ensminger, Stephan M.
AU - Billing, J. Stephen
AU - Morris, Peter J.
AU - Wood, Kathryn J.
PY - 2003/10/15
Y1 - 2003/10/15
N2 - Background. Transplant arteriosclerosis is a major limiting factor for long-term function of allografts in clinical transplantation. This study investigated the impact of three different protocols capable of inducing long-term allograft survival on the development of transplant arteriosclerosis and immune response in cardiac allografts. Methods. CBA.Ca (H2k) recipients of fully allogeneic C57/BL10 (H2b) heart grafts received a short-term course of anti-CD154 antibody or were pretreated with anti-CD4 antibody in combination with donor alloantigen in the form of CBK (H2 k+Kb) bone marrow or C57BL/10 donor-specific transfusion (DST). Grafts were analyzed on day 40 or 100 after transplantation for transplant arteriosclerosis and expression of interferon-γ, interleukin (IL)-2, IL-4, IL-10, IL-12p40, inducible nitric oxide synthase, and transforming growth factor (TGF)-β1 mRNA. Serum was analyzed for the presence of alloantibodies. Results. Intimal proliferation was 62%±11% on day 40 in the anti-CD154 group, progressed from 31%±10% on day 40 to 68%±8% on day 100 in the CBK-bone marrow group, but remained stable at 39%±4% in the DST group. Increased transplant arteriosclerosis on day 100 was associated with high intragraft TGF-β1 mRNA production and eosinophil infiltration, but not alloantibody production. Progressing transplant arteriosclerosis was associated with increased IL-4 expression. Conclusion. Treatment protocols for the induction of long-term allograft survival can differ substantially in the extent and kinetics of transplant arteriosclerosis. IL-4 and TGF-β1 may be two potential therapeutic targets to attenuate the development of transplant arteriosclerosis in the long term.
AB - Background. Transplant arteriosclerosis is a major limiting factor for long-term function of allografts in clinical transplantation. This study investigated the impact of three different protocols capable of inducing long-term allograft survival on the development of transplant arteriosclerosis and immune response in cardiac allografts. Methods. CBA.Ca (H2k) recipients of fully allogeneic C57/BL10 (H2b) heart grafts received a short-term course of anti-CD154 antibody or were pretreated with anti-CD4 antibody in combination with donor alloantigen in the form of CBK (H2 k+Kb) bone marrow or C57BL/10 donor-specific transfusion (DST). Grafts were analyzed on day 40 or 100 after transplantation for transplant arteriosclerosis and expression of interferon-γ, interleukin (IL)-2, IL-4, IL-10, IL-12p40, inducible nitric oxide synthase, and transforming growth factor (TGF)-β1 mRNA. Serum was analyzed for the presence of alloantibodies. Results. Intimal proliferation was 62%±11% on day 40 in the anti-CD154 group, progressed from 31%±10% on day 40 to 68%±8% on day 100 in the CBK-bone marrow group, but remained stable at 39%±4% in the DST group. Increased transplant arteriosclerosis on day 100 was associated with high intragraft TGF-β1 mRNA production and eosinophil infiltration, but not alloantibody production. Progressing transplant arteriosclerosis was associated with increased IL-4 expression. Conclusion. Treatment protocols for the induction of long-term allograft survival can differ substantially in the extent and kinetics of transplant arteriosclerosis. IL-4 and TGF-β1 may be two potential therapeutic targets to attenuate the development of transplant arteriosclerosis in the long term.
UR - http://www.scopus.com/inward/record.url?scp=0142135354&partnerID=8YFLogxK
M3 - Journal articles
C2 - 14557761
AN - SCOPUS:0142135354
VL - 76
SP - 1105
EP - 1111
JO - Cell Transplantation
JF - Cell Transplantation
SN - 0963-6897
IS - 7
ER -