Aberrant T-cell exhaustion in severe combined immunodeficiency survivors with poor T-cell reconstitution after transplantation.

Conditioning chemotherapy T-cell exhaustion hematopoietic cell transplantation (HCT) immune reconstitution severe combined immunodeficiency (SCID)

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
01 2023
Historique:
received: 11 04 2022
revised: 08 08 2022
accepted: 10 08 2022
pmc-release: 01 01 2024
pubmed: 21 8 2022
medline: 11 1 2023
entrez: 20 8 2022
Statut: ppublish

Résumé

Severe combined immunodeficiency (SCID) comprises rare inherited disorders of immunity that require definitive treatment through hematopoietic cell transplantation (HCT) or gene therapy for survival. Despite successes of allogeneic HCT, many SCID patients experience incomplete immune reconstitution, persistent T-cell lymphopenia, and poor long-term outcomes. We hypothesized that CD4 We analyzed markers of exhaustion in blood samples from 61 SCID patients at a median of 10.4 years after HCT. Compared to post-HCT SCID patients with normal CD4 Recipients of unconditioned HCT for SCID may develop late post-HCT T-cell exhaustion as a result of diminished production of T-lineage cells. Elevated expression of inhibitory receptors on their T cells may be a biomarker of poor long-term T-cell reconstitution.

Sections du résumé

BACKGROUND
Severe combined immunodeficiency (SCID) comprises rare inherited disorders of immunity that require definitive treatment through hematopoietic cell transplantation (HCT) or gene therapy for survival. Despite successes of allogeneic HCT, many SCID patients experience incomplete immune reconstitution, persistent T-cell lymphopenia, and poor long-term outcomes.
OBJECTIVE
We hypothesized that CD4
METHODS
We analyzed markers of exhaustion in blood samples from 61 SCID patients at a median of 10.4 years after HCT.
RESULTS
Compared to post-HCT SCID patients with normal CD4
CONCLUSIONS
Recipients of unconditioned HCT for SCID may develop late post-HCT T-cell exhaustion as a result of diminished production of T-lineage cells. Elevated expression of inhibitory receptors on their T cells may be a biomarker of poor long-term T-cell reconstitution.

Identifiants

pubmed: 35987350
pii: S0091-6749(22)01057-0
doi: 10.1016/j.jaci.2022.08.004
pmc: PMC9924130
mid: NIHMS1831997
pii:
doi:

Substances chimiques

Receptors, Antigen, T-Cell 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

260-271

Subventions

Organisme : NIAID NIH HHS
ID : R13 AI094943
Pays : United States
Organisme : CIHR
ID : PJYT-175209
Pays : Canada
Organisme : NCI NIH HHS
ID : U24 CA076518
Pays : United States
Organisme : NIAID NIH HHS
ID : U54 AI082973
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL069294
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS064808
Pays : United States
Organisme : NCATS NIH HHS
ID : U01 TR001263
Pays : United States
Organisme : NHLBI NIH HHS
ID : U10 HL069254
Pays : United States
Organisme : CIHR
ID : MOP-130469
Pays : Canada

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Roxane Labrosse (R)

Pediatric Immunology and Rheumatology Division, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.

Ines Boufaied (I)

Cytokines and Adaptive Immunity Laboratory, Sainte-Justine University Hospital Research Center, Montreal, Quebec, Canada.

Benoîte Bourdin (B)

Cytokines and Adaptive Immunity Laboratory, Sainte-Justine University Hospital Research Center, Montreal, Quebec, Canada.

Saideep Gona (S)

Genetics, Genomics, and Systems Biology, Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, Ill.

Haley E Randolph (HE)

Genetics, Genomics, and Systems Biology, Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, Ill.

Brent R Logan (BR)

Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wis.

Sara Bourbonnais (S)

Cytokines and Adaptive Immunity Laboratory, Sainte-Justine University Hospital Research Center, Montreal, Quebec, Canada.

Chloé Berthe (C)

Cytokines and Adaptive Immunity Laboratory, Sainte-Justine University Hospital Research Center, Montreal, Quebec, Canada.

Wendy Chan (W)

Division of Allergy, Immunology, and Blood and Marrow Transplantation, Department of Pediatrics, University of California, San Francisco, and UCSF Benioff Children's Hospital, San Francisco, Calif.

Rebecca H Buckley (RH)

Duke University Medical Center, Durham, NC.

Roberta E Parrott (RE)

Duke University Medical Center, Durham, NC.

Geoffrey D E Cuvelier (GDE)

Manitoba Blood and Marrow Transplant Program, CancerCare Manitoba, University of Manitoba, Winnipeg, Manitoba, Canada.

Neena Kapoor (N)

Blood and Marrow Transplant Program, Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, Calif.

Sharat Chandra (S)

Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Blachy J Dávila Saldaña (BJ)

Division of Blood and Marrow Transplantation, Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC.

Hesham Eissa (H)

Children's Hospital of Colorado, University of Colorado School of Medicine, Aurora, Colo.

Fred D Goldman (FD)

Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, Ala.

Jennifer Heimall (J)

Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, Pa.

Richard O'Reilly (R)

Department of Pediatrics, Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY.

Sonali Chaudhury (S)

Division of Hematology, Oncology, and Stem Cell Transplantation, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Ill.

Edward A Kolb (EA)

Nemours Children's Health, Center for Cancer and Blood Disorders, Wilmington, Del.

Shalini Shenoy (S)

Division of Pediatric Hematology/Oncology, Department of Pediatrics, Washington University School of Medicine, St Louis, Mo.

Linda M Griffith (LM)

Division of Allergy, Immunology, and Transplantation, National Institutes of Health, Bethesda, Md.

Michael Pulsipher (M)

Blood and Marrow Transplant Program, Division of Hematology, Oncology, and Blood and Marrow Transplantation, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, Calif.

Donald B Kohn (DB)

Pediatrics, David Geffen School of Medicine at University of California, Los Angeles, Calif.

Luigi D Notarangelo (LD)

Laboratory of Clinical Immunology and Microbiology, National Institutes of Health, Bethesda, Md.

Sung-Yun Pai (SY)

Immune Deficiency Cellular Therapy Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Md.

Morton J Cowan (MJ)

Division of Allergy, Immunology, and Blood and Marrow Transplantation, Department of Pediatrics, University of California, San Francisco, and UCSF Benioff Children's Hospital, San Francisco, Calif.

Christopher C Dvorak (CC)

Division of Allergy, Immunology, and Blood and Marrow Transplantation, Department of Pediatrics, University of California, San Francisco, and UCSF Benioff Children's Hospital, San Francisco, Calif.

Élie Haddad (É)

Pediatric Immunology and Rheumatology Division, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada.

Jennifer M Puck (JM)

Division of Allergy, Immunology, and Blood and Marrow Transplantation, Department of Pediatrics, University of California, San Francisco, and UCSF Benioff Children's Hospital, San Francisco, Calif.

Luis B Barreiro (LB)

Genetics, Genomics, and Systems Biology, Department of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, Ill.

Hélène Decaluwe (H)

Pediatric Immunology and Rheumatology Division, Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada; Cytokines and Adaptive Immunity Laboratory, Sainte-Justine University Hospital Research Center, Montreal, Quebec, Canada. Electronic address: helene.decaluwe@umontreal.ca.

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