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Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells

2022; Lippincott Williams & Wilkins; Volume: 98; Issue: 13 Linguagem: Inglês

10.1212/wnl.0000000000200013

1526-632X

Namita Goyal, Gérald Coulis, J.L. Duarte, Philip K. Farahat, Ali H. Mannaa, Jonathan Cauchii, Tyler Irani, Nadia Araujo, Leo Wang, Marie Wencel, Vivian Li, Lishi Zhang, Steven A. Greenberg, Tahseen Mozaffar, S. Armando Villalta,

T-cell and B-cell Immunology

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.