Prolongation of kidney allograft survival regulated by indoleamine 2, 3-dioxygenase in immature dendritic cells generated from recipient type bone marrow progenitors.
Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance. In this study, BN rat recipients were pre-injected with donor renal alloantigen-treated recipient iDCs before kidney transplantation. The renal allograft exhibited a lighter renal rejection response, prolonged graft survival time, and an increasing content of CD4+CD25+Foxp3+regulatory T cells (Tregs). Additionally, up-regulated secretion of Th2 cytokines were found in recipient sera post-transplantation. Transfection of si-IDO1 RNA into renal-antigen-treated recipient iDCs reversed these changes, which suggested that IDO channel signaling may be involved in iDC-induced allograft immunotolerance. These results suggested that iDC-induced and IDO-mediated allograft immunotolerance might be a potentially feasible tactic to prolong allograft survival, in addition to immunosuppressive drugs.
Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China.
Ning
N
Na
Department of Urology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China.
Yun
Y
Luo
Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China.
Daqiang
D
Zhao
Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510080, China.
Shicong
S
Yang
Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China.
Liangqing
L
Hong
Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China.
Heng
H
Li
Department of Kidney Transplantation, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province 510630, China.
Bin
B
Miao
Department of Organ Transplant, The First Affiliated Hospital of Sun Yat-sen University, No.58 Zhongshan 2 Road, Guangzhou, Guangdong Province 510080, China. Electronic address: qiujiang082@163.com.
Jiang
J
Qiu
D064591:Allografts / Q000276:immunology; D000818:Animals; D015153:Blotting, Western; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006085:Graft Survival; D006412:Hematopoietic Stem Cells / Q000201:enzymology / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology* / Q000378:metabolism; D016030:Kidney Transplantation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051381:Rats; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014181:Transplantation Immunology / Q000276:immunology*
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase
3-dioxygenase; Dendritic cells; Indoleamine 2; Kidney allograft; T cell; Tolerance