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J Neurosci Res. 1996 Sep 15;45(6):786-94.

Downregulation of IL-10 secretion and enhanced antigen-presenting abilities following HTLV-I infection of T cells.

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  • 1Laboratory of Molecular Immunology, Brigham & Women's Hospital, Boston, Massachusetts, USA.

Abstract

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.

PMID:
8892090
[PubMed - indexed for MEDLINE]
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