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T and NK Cells in IL2RG-Deficient Patient 50 Years After Hematopoietic Stem Cell Transplantation. | LitMetric

T and NK Cells in IL2RG-Deficient Patient 50 Years After Hematopoietic Stem Cell Transplantation.

J Clin Immunol

Department of Pediatrics, Stem Cell Transplantation Program and Laboratory for Pediatric Immunology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, The Netherlands.

Published: August 2022

AI Article Synopsis

  • The first European hematopoietic stem cell transplantation (HSCT) was successfully performed in 1968 on a newborn with IL2RG deficiency using an HLA-matched sibling donor.
  • After 37 years, the patient received a peripheral stem cell boost due to a decline in T and NK cells and persistent HPV warts, leading to a significant renewal of functional NK cells and an increase in diverse naive T-cells.
  • The study highlighted the presence of clonal expansions in memory T-cells linked to HPV, revealing that the patient maintained both functional and diverse immune cell populations nearly 50 years post-HSCT.

Article Abstract

The first successful European hematopoietic stem cell transplantation (HSCT) was performed in 1968 as treatment in a newborn with IL2RG deficiency using an HLA-identical sibling donor. Because of declining naive T and natural killer (NK) cells, and persistent human papilloma virus (HPV)-induced warts, the patient received a peripheral stem cell boost at the age of 37 years. NK and T cells were assessed before and up to 14 years after the boost by flow cytometry. The boost induced renewed reconstitution of functional NK cells that were 14 years later enriched for CD56CD27 NK cells. T-cell phenotype and T-cell receptor (TCR) repertoire were simultaneously analyzed by including TCR Vβ antibodies in the cytometry panel. Naive T-cell numbers with a diverse TCR Vβ repertoire were increased by the boost. Before and after the boost, clonal expansions with a homogeneous TIGIT and PD-1 phenotype were identified in the CD27 and/or CD28 memory population in the patient, but not in the donor. TRB sequencing was applied on sorted T-cell subsets from blood and on T cells from skin biopsies. Abundant circulating CD8 memory clonotypes with a chronic virus-associated CD57KLRG1CX3CR1 phenotype were also present in warts, but not in healthy skin of the patient, suggesting a link with HPV. In conclusion, we demonstrate in this IL2RG-deficient patient functional NK cells, a diverse and lasting naive T-cell compartment, supported by a stem cell boost, and an oligoclonal memory compartment half a century after HSCT.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537207PMC
http://dx.doi.org/10.1007/s10875-022-01279-5DOI Listing

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