Programmed death-1-programmed death-L1 interaction is essential for induction of regulatory cells by intratracreal delivery of alloantigen

被引:32
作者
Aramaki, O
Shirasugi, N
Takayama, T
Shimazu, M
Kitajima, M
Ikeda, Y
Azuma, M
Okumura, K
Yagita, H
Niimi, M
机构
[1] Teikyo Univ, Dept Surg, Itabashi Ku, Tokyo 1738605, Japan
[2] Nihon Univ, Dept Surg 3, Tokyo, Japan
[3] Keio Univ, Dept Surg, Tokyo, Japan
[4] Tokyo Med & Dent Univ, Grad Sch, Dept Mol Immunol, Tokyo, Japan
[5] Juntendo Univ, Dept Immunol, Tokyo, Japan
关键词
D O I
10.1097/01.TP.0000108637.65091.4B
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Programmed death (PD)-1 has been implicated in peripheral tolerance. The authors investigated the roles of PD-1 and its ligands, PD-L1 and PD-L2, in the introduction of regulatory cells by intratracheal delivery of alloantigen. Methods. CBA (H-2(k) mice were pretreated with intratracheal delivery of C57BL/10 (H-2(b)) splenocytes and administration of monoclonal antibody (mAb) specific for PD-1, PD-L1, or PD-L2. Seven days later, C57BL/10 hearts were transplanted into the pretreated CBA mice. Some naive CBA mice underwent adoptive transfer of splenocytes from the pretreated CBA mice and transplantation of C57BL/10 heart. Results. Untreated CBA mice rejected C57BL/10 cardiac grafts acutely (median survival time [MST], 7 days). Pretreatment with intratracheal delivery of C57BL/10 splenocytes prolonged graft survival significantly (MST, 65 days). Administration of control immunoglobulin (Ig) G or anti-PD-L2 mAb did not significantly affect the prolongation (MST, 72 and 68 days, respectively). In contrast, anti-PD-1 or anti-PD-L1 mAb abrogated the prolongation (MST, 18 and 17 days, respectively). Adoptive transfer from mice pretreated with intratracheal delivery of alloantigen plus control IgG or anti-PD-L2 mAb prolonged survival of C57BL/10 grafts in secondary CBA recipients (MST, 72 and 56 days, respectively). However, concurrent administration of anti-PD1, or anti-PD-L1 mAb abrogated prolonged survival after the adoptive transfer (MST, 14 and 20 days, respectively). Conclusions. PD-1-PD-L1 interaction was essential for introduction of regulatory cells by intratracheal delivery of alloantigen.
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页码:6 / 12
页数:7
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