Modulation of tissue resident memory T cells by glucocorticoids after acute cellular rejection in lung transplantation.
Modulation of tissue resident memory T cells by glucocorticoids after acute cellular rejection in lung transplantation.
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DOI：
10.1084/jem.20212059
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发表时间：
2022-04-04
期刊：
影响因子：
--
通讯作者：
McDyer JF
中科院分区：
文献类型：
--
作者：
Snyder ME;Moghbeli K;Bondonese A;Craig A;Popescu I;Fan L;Tabib T;Lafyatis R;Chen K;Trejo Bittar HE;Lendermon E;Pilewski J;Johnson B;Kilaru S;Zhang Y;Sanchez PG;Alder JK;Sims PA;McDyer JF
在肺移植后的急性细胞排斥反应期间，存在细胞毒性CD8+ T细胞的同种异体移植物内寡克隆扩增。尽管用全身性糖皮质激素治疗，但扩增的T细胞克隆仍然是转录重编程的、以气道为中心的组织驻留记忆T细胞。急性细胞排斥反应在肺移植后很常见，并且与早期慢性排斥反应的风险增加有关。我们提出了联合单细胞RNA和TCR测序从支气管肺泡灌洗获得的三个肺移植受者排斥反应的T细胞，并比较它们与T细胞从相同的患者后获得的排斥反应与高剂量全身糖皮质激素治疗。在排斥反应发生时，我们发现细胞毒性CD8+ T细胞的寡克隆扩增，在成功治疗后，这些细胞都作为组织驻留记忆T细胞持续存在。持续的CD8+同种异体移植物驻留T细胞在糖皮质激素治疗后细胞毒性介质的基因表达减少，但在气道周围积聚。这种克隆性扩增与排斥反应时循环T细胞克隆性扩增不一致，表明是原位扩增。因此，我们强调的积累细胞毒性，免疫组织来源的组织驻留记忆T细胞内的肺同种异体移植物，坚持尽管管理的高剂量全身糖皮质激素。这种持续性的长期临床后果尚未得到表征。
During acute cellular rejection after lung transplantation, there is an intra-allograft oligoclonal expansion of cytotoxic CD8+ T cells. Despite treatment with systemic glucocorticoids, expanded T cell clones persist as transcriptionally reprogrammed, airway-centric tissue resident memory T cells. Acute cellular rejection is common after lung transplantation and is associated with an increased risk of early chronic rejection. We present combined single-cell RNA and TCR sequencing on recipient-derived T cells obtained from the bronchoalveolar lavage of three lung transplant recipients with rejection and compare them with T cells obtained from the same patients after treatment of rejection with high-dose systemic glucocorticoids. At the time of rejection, we found an oligoclonal expansion of cytotoxic CD8+ T cells that all persisted as tissue resident memory T cells after successful treatment. Persisting CD8+ allograft-resident T cells have reduced gene expression for cytotoxic mediators after therapy with glucocorticoids but accumulate around airways. This clonal expansion is discordant with circulating T cell clonal expansion at the time of rejection, suggesting in situ expansion. We thus highlight the accumulation of cytotoxic, recipient-derived tissue resident memory T cells within the lung allograft that persist despite the administration of high-dose systemic glucocorticoids. The long-term clinical consequences of this persistence have yet to be characterized.
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影响因子：
46.9
作者：
Becht, Etienne;McInnes, Leland;Newell, Evan W.
通讯作者：
Newell, Evan W.
影响因子：
64.8
作者：
CEPEK, KL;SHAW, SK;BRENNER, MB
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BRENNER, MB
影响因子：
24.8
作者：
Abou-Daya KI;Tieu R;Zhao D;Rammal R;Sacirbegovic F;Williams AL;Shlomchik WD;Oberbarnscheidt MH;Lakkis FG
通讯作者：
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慢性肺同种异体移植功能障碍期间，1型免疫力和内源性免疫调节剂在气道转录组中占主导地位。
DOI：
10.1111/ajt.16360
发表时间：
2021-06
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Iasella CJ;Hoji A;Popescu I;Wei J;Snyder ME;Zhang Y;Xu W;Iouchmanov V;Koshy R;Brown M;Fung M;Langelier C;Lendermon EA;Dugger D;Shah R;Lee J;Johnson B;Golden J;Leard LE;Ellen Kleinhenz M;Kilaru S;Hays SR;Singer JP;Sanchez PG;Morrell MR;Pilewski JM;Greenland JR;Chen K;McDyer JF
通讯作者：
McDyer JF
单细胞RNA测序揭示了T辅助细胞合成从头开始的类固醇，从而有助于免疫稳态。
影响因子：
8.8
作者：
Mahata B;Zhang X;Kolodziejczyk AA;Proserpio V;Haim-Vilmovsky L;Taylor AE;Hebenstreit D;Dingler FA;Moignard V;Göttgens B;Arlt W;McKenzie AN;Teichmann SA
通讯作者：
Teichmann SA