Immunohistochemical Phenotype of T Cells Invading Muscle in Inclusion Body Myositis

Shiro Matsubara, Shigeaki Suzuki, Takashi Komori

Research output: Contribution to journalArticlepeer-review

Abstract

Inclusion body myositis (IBM) is an inflammatory myopathy of aged people with poor response to therapy. To characterize muscle-invading inflammatory cells, we performed immunohistochemical and ultrastructural studies on muscle biopsies from 10 patients with IBM with durations of illness from 3 to 84 months. At the surface of muscle fibers, 79% and 48% of CD8+ cells were positive for killer cell lectin-like receptor subfamily G, member 1 (KLRG1) and CD57, respectively. CD8+KLRG1+ cells are highly differentiated cytotoxic cells. On an average, 27% of CD8-CD57+KLRG1+ cells at the surface were CD4+. Proportions of CD28+ cells among KLRG1+ cells showed a negative correlation with duration of illness (r = -0.68). These changes indicated progressive differentiation of CD8+ T cells. Moreover, PD-1 expression on CD57+ and CD8+ cells increased early, then fluctuated, and reincreased in later stages. PD ligand-1 (PD-L1) and PD-L2 were expressed on adjacent cells including muscle fibers. T cell large granular lymphocytes (LGLs) are potent effector cells and cells with ultrastructure indistinguishable from LGLs were seen in the sarcoplasm along with lymphocytes undergoing degeneration. Together, along the course of IBM, some inflammatory cells retained the potential for cytotoxicity whereas others indicated suppression by exhaustion, senescence, or through the PD-1 pathway.

Original languageEnglish
Pages (from-to)825-835
Number of pages11
JournalJournal of Neuropathology and Experimental Neurology
Volume81
Issue number10
DOIs
Publication statusPublished - 2022 Sep 19

Keywords

  • CD28
  • Inclusion body myositis
  • Inflammatory myopathy
  • KLRG1
  • PD ligands
  • PD-1

ASJC Scopus subject areas

  • Medicine(all)

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