title: Up-regulation of interleukin-12 receptor expression in peripheral blood mononuclear cells of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.
abstract: 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.
authors.affiliation: The First Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, 852-8501, Nagasaki, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujimoto
authors.forename: Tatsufumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishiura
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Ichinose
authors.forename: Takafumi
authors.initials: T
authors.lastname: Furuya
authors.forename: Susumu
authors.initials: S
authors.lastname: Shirabe
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019013:CD40 Antigens / Q000097:blood / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018664:Interleukin-12 / Q000097:blood* / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000097:blood* / Q000276:immunology*; D010641:Phenotype; D012333:RNA, Messenger / Q000097:blood; D018123:Receptors, Interleukin / Q000097:blood / Q000235:genetics / Q000276:immunology; D053707:Receptors, Interleukin-12; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; C508438:IL12RB1 protein, human; C508439:IL12RB2 protein, human; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12