دورية أكاديمية
Mass cytometry reveals single-cell kinetics of cytotoxic lymphocyte evolution in CMV-infected renal transplant patients.
| العنوان: | Mass cytometry reveals single-cell kinetics of cytotoxic lymphocyte evolution in CMV-infected renal transplant patients. |
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| المؤلفون: | Ishiyama K; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143.; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, CA 94143., Arakawa-Hoyt J; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143.; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, CA 94143., Aguilar OA; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143.; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, CA 94143., Damm I; Department of Surgery, University of California, San Francisco, CA 94143., Towfighi P; Department of Surgery, University of California, San Francisco, CA 94143., Sigdel T; Department of Surgery, University of California, San Francisco, CA 94143., Tamaki S; Parnassus Flow Cytometry Core, University of California, San Francisco, CA 94143., Babdor J; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143.; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, CA 94143.; Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, CA 94143., Spitzer MH; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143.; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, CA 94143.; Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, CA 94143.; Chan Zuckerberg Biohub, San Francisco, CA 94158., Reed EF; Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095., Sarwal MM; Department of Surgery, University of California, San Francisco, CA 94143., Lanier LL; Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; lewis.lanier@ucsf.edu.; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, CA 94143. |
| مؤلفون مشاركون: | CMV Systems Immunobiology Group |
| المصدر: | Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2022 Feb 22; Vol. 119 (8). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: National Academy of Sciences Country of Publication: United States NLM ID: 7505876 Publication Model: Print Cited Medium: Internet ISSN: 1091-6490 (Electronic) Linking ISSN: 00278424 NLM ISO Abbreviation: Proc Natl Acad Sci U S A Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, DC : National Academy of Sciences |
| مواضيع طبية MeSH: | Cytomegalovirus Infections/*immunology , Flow Cytometry/*methods , Killer Cells, Natural/*metabolism, Adult ; CD8-Positive T-Lymphocytes/metabolism ; Cell Separation/methods ; Cytomegalovirus/metabolism ; Cytomegalovirus/pathogenicity ; Cytomegalovirus Infections/virology ; Female ; Graft Rejection/immunology ; Humans ; Kidney Transplantation/adverse effects ; Kidney Transplantation/methods ; Killer Cells, Natural/immunology ; Kinetics ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; NK Cell Lectin-Like Receptor Subfamily C/metabolism ; Single-Cell Analysis/methods ; Viremia/immunology ; Viremia/virology |
| مستخلص: | Cytomegalovirus (CMV) infection is associated with graft rejection in renal transplantation. Memory-like natural killer (NK) cells expressing NKG2C and lacking FcεRIγ are established during CMV infection. Additionally, CD8 + T cells expressing NKG2C have been observed in some CMV-seropositive patients. However, in vivo kinetics detailing the development and differentiation of these lymphocyte subsets during CMV infection remain limited. Here, we interrogated the in vivo kinetics of lymphocytes in CMV-infected renal transplant patients using longitudinal samples compared with those of nonviremic (NV) patients. Recipient CMV-seropositive (R+) patients had preexisting memory-like NK cells (NKG2C + CD57 + FcεRIγ - ) at baseline, which decreased in the periphery immediately after transplantation in both viremic and NV patients. We identified a subset of prememory-like NK cells (NKG2C + CD57 + FcεRIγ low-dim ) that increased during viremia in R+ viremic patients. These cells showed a higher cytotoxic profile than preexisting memory-like NK cells with transient up-regulation of FcεRIγ and Ki67 expression at the acute phase, with the subsequent accumulation of new memory-like NK cells at later phases of viremia. Furthermore, cytotoxic NKG2C + CD8 + T cells and γδ T cells significantly increased in viremic patients but not in NV patients. These three different cytotoxic cells combinatorially responded to viremia, showing a relatively early response in R+ viremic patients compared with recipient CMV-seronegative viremic patients. All viremic patients, except one, overcame viremia and did not experience graft rejection. These data provide insights into the in vivo dynamics and interplay of cytotoxic lymphocytes responding to CMV viremia, which are potentially linked with control of CMV viremia to prevent graft rejection. Competing Interests: The authors declare no competing interest. (Copyright © 2022 the Author(s). Published by PNAS.) |
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| معلومات مُعتمدة: | P30 DK063720 United States DK NIDDK NIH HHS; S10 OD018040 United States OD NIH HHS; U19 AI128913 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Investigator: K Ishiyama; J Arakawa-Hoyt; T Sigdel; EF Reed; MM Sarwal; LL Lanier; R Ahn; J Brook; S Bunnapradist; N Datta; M Deng; D Diamond; T Doung; J Gadzhyan; D Elashoff; D Gjertson; V Groysberg; A Hoffman; E Lum; H Pickering; Z Qian; M Ramirez; M Rossetti; D Rychov; J Schaenman; A Schroeder; S Sen; D Sim; M Sirota; F Vicenti; O Yang Keywords: NK cell; cytomegalovirus; cytotoxic lymphocyte; mass cytometry; renal transplantation |
| المشرفين على المادة: | 0 (KLRC2 protein, human) 0 (NK Cell Lectin-Like Receptor Subfamily C) |
| تواريخ الأحداث: | Date Created: 20220219 Date Completed: 20220314 Latest Revision: 20240214 |
| رمز التحديث: | 20240214 |
| مُعرف محوري في PubMed: | PMC8872722 |
| DOI: | 10.1073/pnas.2116588119 |
| PMID: | 35181606 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1091-6490 |
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| DOI: | 10.1073/pnas.2116588119 |