Posttransplant infusion of donor-specific blood induces immunological unresponsiveness in rat hepatic allografts.
BACKGROUND
We previously reported that pretransplant donor-specific blood transfusion (DST) induces CD45RC-CD4+ T cells, Th2-like effector cells, and prolongs rat hepatic allograft survival. Our study investigated the effects of posttransplant DST on rat hepatic allograft survival.


METHODS
Three days after transplantation, LEW (RT1(1)) recipient rats with ACI (RT1a) livers were injected i.v. with freshly heparinized donor-specific blood. The time kinetics of CD45RC-CD4+ and CD45RC+CD4+ T cell subsets in hepatic infiltrates were examined.


RESULTS
Posttransplant DST significantly prolonged rat hepatic allograft survival. Interferon (IFN)-gamma, interleukin (IL)-12, and IL-18 mRNA levels in hepatic allografts of untreated recipients were significantly greater than in recipients treated with posttransplant DST. However, hepatic allografts of recipients treated with posttransplant DST showed significantly higher IL-4, IL-10, and transforming growth factor (TGF)-beta mRNA levels than untreated recipients. The ratio of CD45RC-CD4+ T cells to CD45RC+CD4+ T cells was significantly higher in hepatic allografts treated with posttransplant DST than in untreated animals. Immunostaining with anti-rat dendritic cell (OX-62) monoclonal antibody revealed that OX-62+ cells were distributed to the splenic red pulp of animals treated with posttransplant DST and to the splenic white pulp in untreated animals. Most OX62+ cells isolated from the spleen of recipients treated with posttransplant DST expressed donor RT1Ba class II major histocompatibility complex antigens, suggesting that OX-62+ cells were of donor origin.


CONCLUSIONS
Posttransplant DST was associated with persistent infiltration of CD45RC-CD4+ T cells, Th2-like effector cells, in rat hepatic allografts, causing immunologic unresponsiveness and establishment of microchimerism in the spleen.
Liang
J
J
Department of Surgery II, Kumamoto University Medical School, Japan.
Yamaguchi
Y
Y
Matsuda
T
T
Ohshiro
H
H
Zhang
J L
JL
Okabe
K
K
Matsumura
F
F
Ishihara
K
K
Uchino
S
S
Mori
K
K
Yamada
S
S
Ogawa
M
M
D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D001803:Blood Transfusion; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002469:Cell Separation; D004396:Coloring Agents; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology; D007150:Immunohistochemistry; D017493:Leukocyte Common Antigens / Q000502:physiology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D013154:Spleen / Q000737:chemistry; D013997:Time Factors; D018183:Transplantation Chimera / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
D004396:Coloring Agents; D017493:Leukocyte Common Antigens