Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Transplantation. 2011 Apr 27;91(8):827-32. doi: 10.1097/TP.0b013e31820f0856.
Memory T cells migrate to and reject transplanted organs without the need for priming in secondary lymphoid tissues, but the mechanisms by which they do so are not known. Here, we tested whether CXCR3, implicated in the homing of effector T cells to sites of infection, is critical for memory T-cell migration to vascularized allografts.
CD4 and CD8 memory T cells were sorted from alloimmunized CXCR3 and wildtype B6 mice and cotransferred to congenic B6 recipients of BALB/c heart allografts. Graft-infiltrating T cells were quantitated 20 and 72 hr later by flow cytometry. Migration and allograft survival were also studied in splenectomized alymphoplastic (aly/aly) recipients, which lack secondary lymphoid tissues.
We found that polyclonal and antigen-specific memory T cells express high levels of CXCR3. No difference in migration of wildtype versus CXCR3 CD4 and CD8 memory T cells to allografts could be detected in wildtype or aly/aly hosts. In the latter, wildtype and CXCR3 memory T cells precipitated acute rejection at similar rates. Blocking CCR5, a chemokine receptor also upregulated on memory T cells, did not delay graft rejection mediated by CXCR3 memory T cells.
CXCR3 is not critical for the migration of memory T cells to vascularized organ allografts. Blocking CXCR3 or CXCR3 and CCR5 does not delay acute rejection mediated by memory T cells. These findings suggest that the mechanisms of memory T cell-homing to transplanted organs may be distinct from those required for their migration to sites of infection.
记忆 T 细胞迁移到并排斥移植器官，而无需在次级淋巴组织中进行引发，但它们这样做的机制尚不清楚。在这里，我们测试了 CXCR3 是否与效应 T 细胞向感染部位归巢有关，对于记忆 T 细胞向血管化同种异体移植物的迁移是否至关重要。
从同种异体免疫的 CXCR3 和野生型 B6 小鼠中分离出 CD4 和 CD8 记忆 T 细胞，并将其共转移到 BALB/c 心脏同种异体移植物的同基因 B6 受体中。通过流式细胞术在 20 和 72 小时后定量测定移植物浸润 T 细胞。还在缺乏次级淋巴组织的脾切除术淋巴缺陷（aly/aly）受体中研究了迁移和同种异体移植物存活。
我们发现多克隆和抗原特异性记忆 T 细胞表达高水平的 CXCR3。在野生型或 aly/aly 宿主中，均未检测到野生型与 CXCR3 CD4 和 CD8 记忆 T 细胞向同种异体移植物的迁移差异。在后一种情况下，野生型和 CXCR3 记忆 T 细胞以相似的速度引发急性排斥反应。阻断趋化因子受体 CCR5，该受体也在上调记忆 T 细胞上表达，并没有延迟由 CXCR3 记忆 T 细胞介导的移植物排斥反应。
CXCR3 对于记忆 T 细胞向血管化器官同种异体移植物的迁移并非至关重要。阻断 CXCR3 或 CXCR3 和 CCR5 不会延迟记忆 T 细胞介导的急性排斥反应。这些发现表明，记忆 T 细胞归巢移植器官的机制可能与它们向感染部位迁移的机制不同。
