title: Blockade of IL-2 receptor suppresses HTLV-I and IFN-gamma expression in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis.
abstract: OBJECTIVE
  Th1 activation based on a high HTLV-I proviral load is one of the characteristic immunological abnormalities in the peripheral blood lymphocytes of patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). To clarify the cause of this abnormality with the potential to be one of the therapeutic targets, we analyzed the involvement of interleukin-2 (IL-2)/IL-2 receptor (IL-2R) signaling in HTLV-I and interferon-gamma (IFN-gamma), which is a representative Th1 cytokine, expression in peripheral blood CD4(+) T cells from HAM/TSP patients.
  
  
  METHODS
  Twelve patients with HAM/TSP were included in the study. After the peripheral blood CD4(+) T cells were treated in cultures under the presence of each anti-IL-2Ralpha, beta,and gamma blocking antiboby for 48 hours, both HTLV-I p19 antigen and IFN-gamma levels in the culture supernatants were measured using ELISA methods. To check the influence on cell proliferation under these culture conditions, the numbers of viable cells were simultaneously determined by MTS assay.
  
  
  RESULTS
  Treatment with anti-IL-2Ralpha blocking antibody, but not anti-IL-2Rbeta or anti-IL-2Rgamma blocking antibody, suppressed HTLV-I p19 antigen expression levels. In addition, treatment with all types of anti-IL-2R blocking antibodies also suppressed IFN-gamma expression levels. All of the types of anti-IL-2R blocking antibodies did not inhibit the proliferation.
  
  
  CONCLUSIONS
  These results indicate that IL-2/IL-2R signaling is involved in HTLV-I and IFN-gamma expression on peripheral blood CD4(+) T cells from HAM/TSP patients, suggesting that the interruption of this signaling has therapeutic potential against HAM/TSP in patients with the focus on the down-regulation of Th1 activation based on a high HTLV-I proviral load in the peripheral blood.
authors.affiliation: Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Naomi
authors.initials: N
authors.lastname: Fukushima
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishiura
authors.forename: Tatsufumi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.forename: Katsumi
authors.initials: K
authors.lastname: Eguchi
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D005260:Female; D015486:HTLV-I Antigens / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000097:blood / Q000276:immunology* / Q000821:virology*; D011336:Probability; D015375:Receptors, Interleukin-2 / Q000187:drug effects / Q000276:immunology*; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D015398:Signal Transduction
chemical_list: D000998:Antiviral Agents; D015486:HTLV-I Antigens; D015375:Receptors, Interleukin-2; D007371:Interferon-gamma