Increased CD4+CD25+Foxp3+ regulatory T cells in tolerance induced by portal venous injection.
BACKGROUND
A portal vein injection (PVI) of allogeneic donor antigen is known to prolong the survival of a subsequently transplanted allograft; however, the underlying mechanism remains to be clarified.


METHODS
Irradiated C57BL/6 (B6) splenocytes were injected into BALB/c mice via the portal vein. Seven days after injection, the proportions of CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells were determined in the blood, liver, and spleen. CD4(+) and CD8(+) T cells were isolated from BALB/c mice that received PVI of B6 splenocytes (PVI mice), adoptively transferred into recipient BALB/c mice 1 day before B6 or third-party C3H heart transplantation, and graft survival was compared. B6 or C3H heart allografts were implanted into anti-CD25 monoclonal antibody (mAb)-treated PVI and untreated PVI mice, and graft survivals were compared. The percentages of CD4(+)CD25(+)Foxp3(+) Treg, cytokine profiles, and ratios of apoptosis were determined in anti-CD25 mAb-treated PVI and untreated PVI mice.


RESULTS
PVI of allogeneic cells induced antigen-specific tolerance and increased the percentage of CD4(+)CD25(+)Foxp3(+) Treg. Adoptive transfer of CD4(+) T cells, but not CD8(+) T cells, from PVI mice prolonged B6 heart allograft survival. Depletion of CD4(+)CD25(+) T cells prevented the induction of tolerance and decreased the percentage of CD4(+)CD25(+)Foxp3(+) Treg in the CD3(+) T-cell pool, and thus was associated with decreased production of interleukin (IL)-4 and apoptosis of T cells.


CONCLUSIONS
Increased CD4(+)CD25(+)Foxp3(+) Treg play an important role in portal vein tolerance induction, at least partly via increasing the production of IL-4 and decreasing apoptosis of T cells.
He
Fan
F
Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chen
Zhishui
Z
Xu
Shengyuan
S
Cai
Ming
M
Wu
Min
M
Li
Hongzhou
H
Chen
Xiaoping
X
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006085:Graft Survival; D016027:Heart Transplantation / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology; D007275:Injections, Intravenous / Q000379:methods*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D011169:Portal Vein / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology
D015703:Antigens, CD; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit; D015847:Interleukin-4