The extent to which tissue-resident memory T (T) cells in transplanted organs possess alloreactivity is uncertain. This study investigates the alloreactive potential of T cells in kidney explants from 4 patients who experienced severe acute rejection leading to graft loss. Alloreactive T cell receptor (TCR) clones were identified in pretransplant blood samples through mixed lymphocyte reactions, followed by single-cell RNA and TCR sequencing of the proliferated recipient T cells. Subsequently, these TCR clones were traced in the T cells of kidney explants, which were also subjected to single-cell RNA and TCR sequencing. The proportion of recipient-derived T cells expressing an alloreactive TCR in the 4 kidney explants varied from 0% to 9%. Notably, these alloreactive TCRs were predominantly found among CD4+ and CD8+ T cells with an effector phenotype. Intriguingly, these clones were present not only in recipient-derived T cells but also in donor-derived T cells, constituting up to 4% of the donor population, suggesting the presence of self-reactive T cells. Overall, our study demonstrates that T cells with alloreactive potential present in the peripheral blood prior to transplantation can infiltrate the kidney transplant and adopt a T phenotype.

中文翻译：

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人肾移植中的组织驻留记忆 T 细胞具有同种异体反应潜力

移植器官中组织驻留记忆 T (T) 细胞具有同种异体反应性的程度尚不确定。本研究调查了 4 名经历过严重急性排斥反应并导致移植物丢失的患者的肾外植体中 T 细胞的同种反应潜力。通过混合淋巴细胞反应，随后对增殖的受体 T 细胞进行单细胞 RNA 和 TCR 测序，在移植前血样中鉴定出同种异体反应性 T 细胞受体 (TCR) 克隆。随后，在肾脏外植体的 T 细胞中追踪这些 TCR 克隆，并对其进行单细胞 RNA 和 TCR 测序。在 4 个肾外植体中，表达同种异体反应性 TCR 的受体来源 T 细胞的比例从 0% 到 9% 不等。值得注意的是，这些同种异体反应性 TCR 主要存在于具有效应表型的 CD4+ 和 CD8+ T 细胞中。有趣的是，这些克隆不仅存在于受者来源的 T 细胞中，而且也存在于供者来源的 T 细胞中，占供者群体的 4%，表明存在自身反应性 T 细胞。总体而言，我们的研究表明，移植前外周血中存在的具有同种异体反应潜力的 T 细胞可以浸润肾移植物并采用 T 表型。