Essential role of sphingosine-1-phosphate receptor 1-bearing CD8+CD44+CCR7+ T cells in acute skin allograft rejection.
A subset of naturally formed sphingosine-1-phosphate receptor 1 (S1P1)-bearing CD8(+)CD44(+)CCR7(+) memory T cells has been identified in transplant recipient BALB/c (H-2(d)) mice. The frequency of this subset of memory T cells is significantly increased in the spleen, lymph nodes and skin grafts in the recipient BALB/c mice during acute skin allograft rejections. The immune-reconstitution with CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cells facilitates acute skin allograft rejection in SCID mice. Being Th1-polarized and cytotoxic, CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cells proliferate and differentiate immediately into effectors upon encountering allo-antigens. A siRNA against S1P1 inhibits CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cell-mediated acute skin allograft rejection in SCID mice by means of knocking-down S1P1-expression. CCL21 mutant (CCL21-DeltaCT) has been used to compete with wild-type CCL21 in the course of binding to CCR7. Combined administration of siRNA S1P1 and CCL21-DeltaCT significantly prolongs the survival of skin allograft in the recipient BALB/c mice by means of inhibiting accumulation of CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cells in the spleen and the skin grafts. Our data provide direct evidence that S1P1 and CCR7 are involved in the proliferation and trafficking of CD8(+)CD44(+)CCR7(+)S1P1(+) memory T cells. S1P1 may serve as a functional marker for CD8(+)CD44(+)CCR7(+) memory T cells. Targeting CD8(+)CD44(+)CCR7(+)S1P1(+) T cells may be a useful strategy to prolong the survival of allograft transplant.
Department of Immunology, and Laboratory of Allergy and Clinical Immunology, Institute of Allergy and Immune-Related Diseases and Center for Medical Research, Wuhan University School of Medicine, Wuhan, China.
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H
Yuling
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Ruijing
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J
Xiang
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Luokun
Y
Y
Wenjun
C
C
Feng
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H
Baojun
Y
Y
Hui
Y
Y
Guang
Y
Y
Chunlei
Z
Z
Jixin
C
C
Lang
Q
Q
Li
A
A
Chang
B
B
Zhuan
J
J
Youxin
G
G
Feili
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Jinquan
D000818:Animals; D016827:CD8 Antigens / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D054400:Receptors, CCR7 / Q000032:analysis; D049349:Receptors, Lysosphingolipid / Q000276:immunology*; D016038:Skin Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014184:Transplantation, Homologous
D016827:CD8 Antigens; C515371:Ccr7 protein, mouse; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D054400:Receptors, CCR7; D049349:Receptors, Lysosphingolipid