CD40-CD40L costimulation blockade induced the tolerogenic dendritic cells in mouse cardiac transplant.
We aimed to investigate whether tolerogenic dendritic cells (DCs) were induced in the tolerant recipients with the blockade of CD40-CD40L costimulation. Mouse heterotopic heart transplantation was performed. DCs were sorted from rejected and tolerant recipients using magnetic-activated cell sorting. Their expression of CD40, CD80, and CD86 was examined using fluorescence-activated cell sorting. DCs were stimulated with lipopolysaccharide in vitro, and interleukin 10 (IL-10) and IL-12 levels in the supernatants were evaluated using enzyme-linked immunosorbent assay. By using mixed leukocyte reaction, we investigated the stimulatory capacities and tolerogenic capability of DCs. DCs from tolerant recipients expressed lower level of costimulatory molecules, including CD40, CD80, and CD86 and released higher levels of IL-10 and lower levels of IL-12. In addition, DCs from tolerant recipients were weak stimulators of the mixed leukocyte reaction and inhibited the proliferation of splenocytes. IL-10(high)IL-12(low) DCs with immature phenotype were induced in the tolerant recipients with the blockade of CD40-CD40L costimulation, and they obtained the tolerogenic function.
Jiang
Xiao-Feng
XF
Department of Surgery, the Fourth Affiliated Hospital, China Medical University, Shenyang, China. jiang_xiaofeng@hotmail.com
Cui
Zhe-Ming
ZM
Zhu
Lei
L
Guo
Da-Wei
DW
Sun
Wen-Yu
WY
Lin
Lin
L
Wang
Xue-Fan
XF
Tang
Yu-Fu
YF
Liang
Jian
J
D000818:Animals; D019013:CD40 Antigens / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000276:immunology*; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023001:Transplantation Tolerance / Q000276:immunology*
D019013:CD40 Antigens; D016753:Interleukin-10; D023201:CD40 Ligand; D018664:Interleukin-12