Up-regulation of interleukin-12 receptor expression in peripheral blood mononuclear cells of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.
We previously reported elevated levels of serum interleukin-12 (IL-12) in association with increased interferon-gamma (IFN-gamma) levels in patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/ TSP). The interaction between IL-12 and IL-12 receptor (IL-12R) plays an important role in differentiation of the T helper type 1 (Th1) phenotype. In this study, we further examined the IL-12/IL-12R axis by investigating the expression of IL-12R and CD40 ligand (CD40L) in peripheral blood mononuclear cells (PBMC) of 18 HAM/ TSP patients, and comparing the levels with those in 25 patients with other neurological disorders, including 4 anti-HTLV-I-seropositive carriers as controls. Two-color analysis by flow cytometry revealed a significantly high percentage of IL-12R beta1+ cells in CD4+ T lymphocytes in HAM/ TSP patients compared to the control. Furthermore, IL-12R beta2 mRNA expression in PBMC was detected by reverse-transcriptase polymerase chain reaction in 6 of 18 HAM/ TSP patients, but not in any control patients. In contrast, there was no significant difference between the percentage of CD40L+ cells in CD4+ T lymphocytes in HAM/ TSP and control patients. Our results suggest Th1 immune activation in patients with HAM/ TSP, which leads to chronic inflammation in the spinal cord, mediated by dysregulation of the IL-12/IL-12R axis rather than of the CD40/CD40L interaction.[1]References
- Up-regulation of interleukin-12 receptor expression in peripheral blood mononuclear cells of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis. Fujimoto, T., Nakamura, T., Nishiura, Y., Ichinose, K., Furuya, T., Shirabe, S., Eguchi, K. J. Neurol. Sci. (2002) [Pubmed]
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