Cardiac allograft tolerance induced by isogeneic CD4+CD25+ regulatory T cells.
OBJECTIVE
To evaluate the effect of isogeneic CD4+CD25+ regulatory T cells on cardiac allograft tolerance in heterotopic heart transplant from Balb/c to C57BL/6 mice.


METHODS
Isogeneic and allogeneic CD4+CD25+ regulatory T cells were obtained from pregnant C57BL/6 mice crossed with male Balb/c mice and from regular Balb/c mice. Recipient C57BL/6 mice were treated with sublethal radiation (2 Gy) and an infusion of isogeneic CD4+CD25+ regulatory T cells, allogeneic CD4+CD25+ regulatory T cells, or phosphate-buffered saline alone 1 day before a Balb/c-to-C57BL/6 heterotopic heart transplant. At 10 days after the transplant, cardiac allografts and the sera of recipients were evaluated with histology and cytokine analysis. Splenocytes of recipients were collected to determine chimerism on the day of the cessation of allograft heartbeat.


RESULTS
Mice that received an infusion of isogeneic CD4+CD25+ regulatory T cells had significantly greater mean median survival time, greater degree of chimerism, decreased levels of cytokines (monokine induced by interferon-γ, interleukin 6, interleukin 10, and regulated upon activation, normal T cell expressed and secreted protein), and decreased lymphocytic infiltration than did mice that received phosphate-buffered saline alone. The effects on allograft tolerance were stronger in mice that received the isogeneic than the allogeneic CD4+CD25+ regulatory T cells.


CONCLUSIONS
Isogeneic CD4+CD25+ regulatory T cells may establish cardiac allograft tolerance by inducing mixed chimerism and suppressing immune responses. Infusion with isogeneic CD4+CD25+ regulatory T cells combined with radiation (sublethal dose, 2 Gy) may establish allograft tolerance in mice. Therefore, further study is warranted because isogeneic CD4+CD25+ regulatory T cells may have therapeutic benefits.
Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.
Xiaoqian
X
Lu
Xian
X
Yang
Qin
Q
Zhou
Yuchen
Y
Wang
Shi
S
Feng
Juan
J
Jin
Xiujing
X
Shen
Chuan
C
Lin
Hong
H
Jiang
Jianghua
J
Chen
D064591:Allografts; D000818:Animals; D016207:Cytokines / Q000097:blood; D005260:Female; D006085:Graft Survival; D016027:Heart Transplantation; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000276:immunology*; D064596:Isografts; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D013997:Time Factors; D018183:Transplantation Chimera; D023001:Transplantation Tolerance
D016207:Cytokines; C508018:Il2ra protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit