UC Irvine

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.