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Abstract
Background and Objectives To evaluate the therapeutic potential of targeting highly differentiated T cells in patients with inclusion body myositis (IBM) by establishing high-resolution mapping of killer cell lectin-like receptor subfamily G member 1 (KLRG1+) within the T and natural killer (NK) cell compartments.
Methods Blood was collected from 51 patients with IBM and 19 healthy age-matched donors. Peripheral blood mononuclear cells were interrogated by flow cytometry using a 12-marker antibody panel. The panel allowed the delineation of naive T cells (Tn), central memory T cells (Tcm), 4 stages of effector memory differentiation T cells (Tem 1–4), and effector memory re-expressing CD45RA T cells (TemRA), as well as total and subpopulations of NK cells based on the differential expression of CD16 and C56.
Results We found that a population of KLRG1+ Tem and TemRA were expanded in both the CD4+ and CD8+ T-cell subpopulations in patients with IBM. KLRG1 expression in CD8+ T cells increased with T-cell differentiation with the lowest levels of expression in Tn and highest in highly differentiated TemRA and CD56+CD8+ T cells. The frequency of KLRG1+ total NK cells and subpopulations did not differ between patients with IBM and healthy donors. IBM disease duration correlated with increased CD8+ T-cell differentiation.
Discussion Our findings reveal that the selective expansion of blood KLRG1+ T cells in patients with IBM is confined to the TemRA and Tem cellular compartments.
Glossary
- ATG=
- anti-T-lymphocyte globulin;
- CPT=
- cell preparation tube;
- ENMC=
- European Neuromuscular Centre;
- FACS=
- fluorescence-activated cell sorting;
- HC=
- healthy control;
- hPBMC=
- human peripheral blood mononuclear cell;
- IBM=
- inclusion body myositis;
- IBMFRS=
- Inclusion Body Myositis Functional Rating Scale;
- KLRG1=
- killer cell lectin-like receptor subfamily G member 1;
- NK=
- natural killer;
- Tcm=
- central memory T cells;
- Tconv=
- conventional T cells;
- Teff=
- effector T cells;
- Tem=
- effector memory T cells;
- TemRA=
- effector memory re-expressing CD45RA cells;
- Tn=
- naive T cells;
- Treg=
- regulatory T cell
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally as co–senior authors.
Editorial, page 521
- Received July 21, 2021.
- Accepted in final form January 3, 2022.
- © 2022 American Academy of Neurology
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