Cultured lymphocytes' mitochondrial genome integrity is not altered by cladribine

Clin Exp Immunol. 2023 Oct 20:uxad112. doi: 10.1093/cei/uxad112. Online ahead of print.ABSTRACTCladribine tablets are a treatment for multiple sclerosis with effects on lymphocytes, yet its mode of action has not been fully established. Here, we analyzed the effects of cladribine on mitochondrial DNA integrity in lymphocytes. We treated cultured human T-cell lines (CCRF-CEM and Jurkat) with varying concentrations of cladribine to mimic the slow cell depletion observed in treated patients. The CCRF-CEM was more susceptible to cladribine than Jurkat cells. In both cells mitochondrial protein synthesis, mitochondrial DNA copy number and mitochondrial cytochrome-c oxidase-I mRNA mutagenesis was not affected by cladribine, while caspase-3 cleavage was detected in Jurkat cells at 100 nM concentration. Cladribine treatment at concentrations up to 10 nM in CCRF-CEM and 100 nM in Jurkat cells did not induce significant increase in mitochondrial DNA mutations. Peripheral blood mononuclear cells from 8 multiple sclerosis patients and 4 controls were cultured with or without an effective dose of cladribine (5 nM). However, we did not find any differences in mitochondrial DNA somatic mutations in lymphocyte subpopulations (CD4+, CD8+ and CD19+) between treated vs. non-treated cells. The overall mutation rate was similar in patients and controls. When different lymphocyte subpopulations were compared, greater mitochondrial DNA mutation levels were detected in CD8+ (p=0.014) and CD4+ (p=0.0...
Source: Clinical and Developmental Immunology - Category: Allergy & Immunology Authors: Source Type: research