myelin-basic-protein and HTLV-I-Infections

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) is a chronic inflammatory disease that primarily affects the spinal cord and may be a neurological syndrome that is clinically similar to multiple sclerosis (MS). Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of MS patents is generally measured by radioimmunoassay. We have recently established a sensitive enzyme-linked immunosorbent assay (ELISA) and measured the MBP concentrations in CSF and serum of HAM/TSP patients.. A sensitive two-site ELISA capable of measuring MBP at a concentration as low as 30 pg/mL in serum and CSF samples was used.. Significantly higher CSF MBP concentrations were detected in 61% of HAM/TSP patients than in patients with non-neurological diseases. Serum MBP concentrations were also higher in 9% of HAM/TSP patients compared with patients with non-neurological diseases or healthy controls.. Using our ELISA system, we detected MBP in CSF and serum not only in patients with central active demyelination as in MS, but also in patients with spinal cord demyelination as in HAM/TSP.

Topics: Adult; Aged; Animals; Biomarkers; Cattle; Enzyme-Linked Immunosorbent Assay; Female; HTLV-I Infections; Humans; Male; Middle Aged; Myelin Basic Protein; Paraparesis, Tropical Spastic; Radioimmunoassay; Reference Standards; Sensitivity and Specificity

Human T-cell lymphotropic virus type I (HTLV-I) may infect up to 10% of peripheral blood T cells in patients with HTLV-I myelopathy. To examine the impact of HTLV-I infection on the abilities of T cells to present and respond to peptide antigen, we HTLV-I infected and subcloned a myelin basic protein peptide 84-102 (MBP p84-102)-specific T-cell clone. The HTLV-I-infected subclones displayed spontaneous clonal proliferation, as observed in T-cell clones from HTLV-I myelopathy patients, indicating virally induced T-cell activation. In the presence of soluble peptide antigen, the HTLV-I-infected T cells responded to a 100-fold lower peptide concentration than did the uninfected parental T-cell clone. This response was not mediated by virally induced priming for hyperresponsiveness because peptide-pulsed Epstein-Barr Virus (EBV)-transformed B cells or HLA-DR2/B7-1 or B7-2 transfected Chinese hamster ovary (CHO) cells activated uninfected T cells at least twofold better than HTLV-I-infected T cells. Instead, the HTLV-I-infected T cells were better antigen-presenting cells when compared to activated, uninfected T cells and the enhanced ability to present antigen correlated with a marked upregulation in surface expression of major histocompatibility complex (MHC) class II and LFA-3. The ability of HTLV-I-infected T cells to activate other T cells was not simply caused by their state of activation. In contrast with activated and uninfected parental T cells, HTLV-I-infected T cells had downregulated secretion of the immunosuppressive cytokine IL-10, whereas interferon-gamma secretion was significantly increased. Because IL-10 inhibits human CD8 T-cell proliferation, the enhanced antigen-presenting abilities of HTLV-I-infected T cells and the downregulation of IL-10 may be important contributors to the general immune activation and potentially to the remarkably high frequency of cytotoxic T cells observed in HTLV-I myelopathy patients.

Topics: Animals; Antigen Presentation; CHO Cells; Clone Cells; Cricetinae; Down-Regulation; Epitopes; Epitopes, T-Lymphocyte; Histocompatibility Antigens Class II; HTLV-I Infections; Humans; Immune Tolerance; Interleukin-10; Lymphocyte Activation; Myelin Basic Protein; Solubility; T-Lymphocytes; Up-Regulation