Cell-mediated immunomodulation of chemokine receptor 7-expressing porcine sertoli cells in murine heterotopic heart transplantation.
BACKGROUND
Sertoli cells (SC) have immunomodulative properties, and chemokine receptor 7 (CCR7) can optimize the systemic immunomodulatory effect by guiding SC from the periphery to the secondary lymphoid organs.


METHODS
The effect of immortalized neonatal porcine SC (NPSCi) was evaluated by analysis of cytokine levels. Hyporesponsiveness to donor cells was determined by MLC and analysis of splenocyte phenotypes using a murine allogeneic skin graft model. The effect of CCR7-expressing NPSCi (NPSCi-CCR7) combined with cobra venom factor (CVF) was evaluated using a heterotopically transplanted murine allogeneic heart model.


RESULTS
Expression of immune cytokines was markedly modulated by NPSCi. The lymphocyte proliferation and splenocyte phenotypes were significantly suppressed by NPSCi-CCR7. Although pre-transplantation of NPSCi or NPSCi-CCR7 did not prolong graft survival of allogeneic cardiac grafts, CVF treatment facilitated pre-transplantation of NPSCi-CCR7 to prolong survival of allogeneic cardiac grafts (25.5 +/- 7.05 vs 9.5 +/- 0.58 days, p < 0.01).


CONCLUSIONS
NPSCi may be used as a powerful immunomodulatory tool, and our strategy to traffic NPSCi to lymphoid organs using CCR7 optimizes the systemic immunomodulatory effect in vivo. With the help of initial immunosuppression for humoral mechanisms using CVF, the host immune response against allogeneic cardiac grafts can be effectively ameliorated by immunomodulation of the cellular mechanism with NPSCi-CCR7.
Lim
Hong-Gook
HG
Department of Thoracic and Cardiovascular Surgery, Sejong General Hospital, Sejong Heart Institute, Bucheon, Korea.
Lee
Hak-Mo
HM
Oh
Byoung Chol
BC
Lee
Jeong Ryul
JR
D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D016027:Heart Transplantation / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012708:Sertoli Cells / Q000637:transplantation*; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013552:Swine; D014183:Transplantation, Heterologous; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
C515371:Ccr7 protein, mouse; D007155:Immunologic Factors; D054400:Receptors, CCR7