Emergence of anti-inflammatory monocytes in long-term surviving hosts of IL-10-transduced liver allografts.
We previously reported that transduction of IL-10 to rat liver allografts facilitates survival prolongation after orthotopic liver transplantation (OLT). In the current study, we examined Lewis hosts of IL-10-transduced allografts that had survived longer than 50 days in order to characterize peripheral blood mononuclear cells (PBMC). Phenotype analysis of the PBMC demonstrated an 18-fold increase in monocytes (CD11b/c(+)) with a massive increase in the monocyte/lymphocyte ratio. The monocytes expressed downregulated MHC class II (RT1B) but upregulated Fcgamma receptors in comparison with monocytes from the control hosts. The capacity of enriched monocytes to secrete TNF-alpha in response to LPS stimulation was downregulated in the survivors, while production of IL-10 was comparable. The monocytes from long-term survivors significantly inhibited the donor antigen stimulated secretion of IFN-gamma and IL-2. Monocytosis characterized by a shift to anti-inflammatory monocytes is associated with survival prolongation in the hosts of IL-10 transduced liver allografts.
Fan
X H
XH
Department of Surgery II, Hiroshima University Faculty of Medicine, Hiroshima, Japan.
Hayamizu
K
K
Yahata
H
H
Shinozaki
K
K
Tashiro
H
H
Sakaguchi
T
T
Ito
H
H
Asahara
T
T
D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage; D006085:Graft Survival / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007249:Inflammation / Q000235:genetics / Q000517:prevention & control; D007275:Injections, Intravenous; D016753:Interleukin-10 / Q000008:administration & dosage / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology* / Q000401:mortality*; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016019:Survival Analysis; D014161:Transduction, Genetic; D014184:Transplantation, Homologous / Q000276:immunology* / Q000401:mortality*
D016207:Cytokines; D016753:Interleukin-10