Differences in lymphocyte gene expression between tolerant and syngeneic liver grafted rats.
Induction of tolerance to allogeneic donor grafts is a clinically desirable goal in bone marrow and solid organ transplantation. We have taken the advantage of DNA microarray technology to investigate gene expression mechanism in regulatory cells. In the present study, using a tacrolimus (FK506) induced tolerance of the fully mismatched liver allograft rat model, we demonstrated that, in contrast with peripheral blood lymphocytes (PBLs) from syngeneic recipients, PBLs taken from tolerant recipients 100 days after transplantation were able to suppress the in vitro proliferation of allogeneic PBLs and to prolong the survival of second syngeneic recipients. We also compared messenger RNA profiles in PBLs from tolerant recipients with those from syngeneic recipients using a DNA microarray with probe sets corresponding to more than 8000 rat genes. There were 96 up-regulated and 103 down-regulated genes in the tolerant recipients. In the up-regulated group, there were 76 known genes and 20 expressed sequence tags (ESTs). In the down-regulated groups, there were 87 known genes and 16 ESTs. Our data indicated that FK506 treatment induced tolerance and expansion of regulatory cells and the DNA microarray technology was useful for this application and provided many informative insights into the mechanism of lymphocyte regulation.
Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan.
Masayuki
M
Fujino
Yusuke
Y
Kitazawa
Mikiko
M
Kawasaki
Naoko
N
Funeshima
Hiromitsu
H
Kimura
Toshiharu
T
Nakajima
Hirohisa
H
Saito
Xiao-Kang
XK
Li
D000818:Animals; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016031:Liver Transplantation / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology; D008297:Male; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger; D051381:Rats; D016559:Tacrolimus / Q000494:pharmacology; D023001:Transplantation Tolerance / Q000235:genetics* / Q000276:immunology; D014185:Transplantation, Isogeneic
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016559:Tacrolimus