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

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 CD56dimCD27+ 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 CD57+KLRG1+CX3CR1+ 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.

Identification of potential biomarkers of leprosy: A study based on GEO datasets

“…CD48 is involved in a wide variety of innate and adaptive immune responses, including T cell activation, autoimmunity, granulocyte activity, NK function and antimicrobial immunity [ 47 ]. IL2RG plays an essential role in T cells and natural killer (NK) cells production and B cells normal function [ 48 ]. CCR5 can regulate IL-2 production and promote T cell proliferation [ 49 ].…”

Single-cell transcriptomics in bone marrow delineates CD56dimGranzymeK+ subset as intermediate stage in NK cell differentiation

“…No difference in phenotype of CD56 dim GzmK + cells between blood and bone marrow was found (Figure S4C). Interestingly, in an IL2RG deficient patient who received a hematopoietic stem cell transplantation (HSCT) more than 50 years ago and is affected with chronic HPV disease, 26% of the CD56 dim NK cells expressed granzyme K and CD27 (Figure 4F) (72). While a s i m i l a r C D 5 6 d i m C D 2 7 + s u b p o p u l a t i o n w i t h a GzmK + NKG2A high CD16 low TIGIT high KLRG1 high phenotype was also present at a low frequency in healthy controls, it was significantly expanded in this post HSCT patient (Figures 4D-F).…”