دورية أكاديمية
أعرض في EDS

Heterogeneity in allospecific T cell function in transplant-tolerant hosts determines susceptibility to rejection following infection.

التفاصيل البيبلوغرافية
العنوان: Heterogeneity in allospecific T cell function in transplant-tolerant hosts determines susceptibility to rejection following infection.
المؤلفون: McIntosh CM; Department of Medicine, Section of Rheumatology., Allocco JB; Department of Medicine, Section of Rheumatology., Wang P; Department of Medicine, Section of Rheumatology., McKeague ML; Department of Medicine, Section of Rheumatology., Cassano A; Department of Medicine, Section of Rheumatology., Wang Y; Department of Medicine, Section of Rheumatology., Xie SZ; Department of Medicine, Section of Rheumatology., Hynes G; Department of Surgery, Section of Transplantation, and., Mora-Cartín R; Department of Medicine, Section of Rheumatology., Abbondanza D; Department of Medicine, Section of Rheumatology., Chen L; Department of Medicine, Section of Rheumatology., Sattar H; Department of Pathology, University of Chicago, Chicago, Illinois, USA., Yin D; Department of Surgery, Section of Transplantation, and., Zhang ZJ; Comprehensive Transplant Center and.; Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Chong AS; Department of Surgery, Section of Transplantation, and., Alegre ML; Department of Medicine, Section of Rheumatology.
المصدر: The Journal of clinical investigation [J Clin Invest] 2023 Nov 01; Vol. 133 (21). Date of Electronic Publication: 2023 Nov 01.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: CD4-Positive T-Lymphocytes* , Heart Transplantation*, Mice ; Animals ; Transplantation, Homologous ; Transplantation Tolerance ; Graft Rejection/genetics ; Histocompatibility Antigens Class I ; Peptides ; Isoantigens
مستخلص: Even when successfully induced, immunological tolerance to solid organs remains vulnerable to inflammatory insults, which can trigger rejection. In a mouse model of cardiac allograft tolerance in which infection with Listeria monocytogenes (Lm) precipitates rejection of previously accepted grafts, we showed that recipient CD4+ TCR75 cells reactive to a donor MHC class I-derived peptide become hypofunctional if the allograft is accepted for more than 3 weeks. Paradoxically, infection-induced transplant rejection was not associated with transcriptional or functional reinvigoration of TCR75 cells. We hypothesized that there is heterogeneity in the level of dysfunction of different allospecific T cells, depending on duration of their cognate antigen expression. Unlike CD4+ TCR75 cells, CD4+ TEa cells specific for a peptide derived from donor MHC class II, an alloantigen whose expression declines after transplantation but remains inducible in settings of inflammation, retained function in tolerant mice and expanded during Lm-induced rejection. Repeated injections of alloantigens drove hypofunction in TEa cells and rendered grafts resistant to Lm-dependent rejection. Our results uncover a functional heterogeneity in allospecific T cells of distinct specificities after tolerance induction and reveal a strategy to defunctionalize a greater repertoire of allospecific T cells, thereby mitigating a critical vulnerability of tolerance.
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معلومات مُعتمدة: T32 HD007009 United States HD NICHD NIH HHS; P30 CA014599 United States CA NCI NIH HHS; T32 HL007237 United States HL NHLBI NIH HHS; T32 AI007090 United States AI NIAID NIH HHS; P01 AI097113 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: Adaptive immunity; Transplantation
المشرفين على المادة: 0 (Histocompatibility Antigens Class I)
0 (Peptides)
0 (Isoantigens)
تواريخ الأحداث: Date Created: 20230907 Date Completed: 20231102 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10617766
DOI: 10.1172/JCI168465
PMID: 37676735
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI168465