Upregulated inducible co-stimulator (ICOS) and ICOS-ligand in inclusion body myositis muscle: significance for CD8 super(+) T cell cytotoxicity

Interactions between inducible co-stimulatory molecule (ICOS) and ICOS- ligand (ICOS-L) are crucial for T-cell co-stimulation, effector cell differentiation and memory CD8 super(+) T-cell activation. Because in the muscle of patients with sporadic inclusion body myositis (sIBM) clonally expanded CD8 super(+) T cells invade major histocompatibility complex (MHC) class I-expressing muscle fibres, we investigated ICOS super(.)ICOS-L interactions and correlated their expression with perforin, a marker for cytotoxic effector function by autoinvasive CD8 super(+) T cells. The mRNA from 20 muscle biopsies of sIBM, 20 non- inflammatory or dystrophic controls, two dermatomyositis (DM) and two polymyositis (PM) patients was reverse transcribed and reamplified by semi- quantitative and quantitative reverse transcription-polymerase chain reaction (RT-PCR), using primers for ICOS, ICOS-L and perforin. The glyceraldehyde 3- phosphate dehydrogenase (GAPDH)-normalized ratio of ICOS, ICOS-L and perforin expression was compared with the degree of endomysial inflammation. Protein expression of ICOS, ICOS-L and perforin was confirmed by immunohistochemistry. We demonstrate that ICOS-L mRNA was upregulated in sIBM (arbitrary units, median plus or minus SEM: 48.6 plus or minus 14.9) compared with controls (6.2 plus or minus 17.8, P