Essential role of OX40L on B cells in persistent alloantibody production following repeated alloimmunizations
Essential role of OX40L on B cells in persistent alloantibody production following repeated alloimmunizations
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DOI：
10.1023/b:joci.0000025445.21894.e5
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发表时间：
2004-05-01
影响因子：
9.1
通讯作者：
Kobata, T
中科院分区：
文献类型：
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作者：
Kato, H;Kojima, H;Kobata, T
OX 40/OX 40配体（OX 40 L）相互作用以双向方式参与CD 4（+）T和B细胞的共刺激。为了确定OX 40/OX 40 L相互作用在多次同种异体输血后受体抗供体反应中的作用，我们在反复同种异体免疫的OX 40 L缺陷小鼠中检测了同种异体反应性细胞毒性T淋巴细胞（allo-CTL）活性和同种抗体产生。在第五次同种异体免疫后，尽管OX 40 L缺陷型小鼠显示出与野生型小鼠相当的水平的同种异体CTL活性，但OX 40 L缺陷型小鼠中的同种异体抗体产生显著减少，伴随着较少的记忆B和功能降低的CD 4 C T细胞。此外，接受OX 40 L缺陷型T细胞的nu/nu小鼠仍表现出同种抗体产生受损，记忆性CD 4 C T细胞和B细胞较少。相比之下，接受野生型T细胞和OX 40 L缺陷型B细胞的RAG-2缺陷型小鼠产生的同种抗体很少，记忆B细胞较少，但记忆CD 4 C T细胞充足。因此，B细胞上的OX 40 L，而不是T细胞上的OX 40 L，显然是重复同种免疫后同种抗体充分和持续产生所必需的。
OX40/OX40 ligand (OX40L) interactions are implicated in costimulation for both CD4(+) T and B cells in a bidirectional manner. To determine the role of OX40/OX40L interactions in recipient antidonor responses after multiple allogeneic transfusions, we examined alloreactive cytotoxic T lymphocyte (allo-CTL) activity and alloantibody production in repeatedly alloimmunized OX40L-deficient mice. After the fifth alloimmunization, whereas OX40L-deficient mice showed allo-CTL activity with levels comparable to those of wild-type mice, alloantibody production in OX40L-deficient mice was significantly reduced, accompanied by fewer memory B and CD4C T cells with reduced function. Furthermore, nu/nu mice that received OX40L-deficient T cells still exhibited impaired alloantibody production with fewer memory CD4C T and B cells. In contrast, RAG-2-deficient mice that received both wild-type T cells and OX40L-deficient B cells produced scant alloantibodies with fewer memory B cells, but sufficient memory CD4C T cells. Thus, OX40L on B cells, rather than on T cells, is apparently required for adequate and persistent production of alloantibodies after repeated alloimmunizations.