Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells

Abstract

Background and ObjectivesTo 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.MethodsBlood 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.ResultsWe 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.DiscussionOur findings reveal that the selective expansion of blood KLRG1+T cells in patients with IBM is confined to the TemRA and Tem cellular compartments.