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Downregulation of IL‐10 secretion and enhanced antigen‐presenting abilities following HTLV‐I infection of T cells
Author(s) -
Scholz C.,
Hafler D.A.,
Höllsberg P.
Publication year - 1996
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19960915)45:6<786::aid-jnr15>3.0.co;2-u
Subject(s) - antigen , biology , t cell , clone (java method) , cytotoxic t cell , antigen presenting cell , human t lymphotropic virus 1 , virology , cd40 , t lymphocyte , interleukin 21 , major histocompatibility complex , microbiology and biotechnology , immunology , virus , immune system , in vitro , t cell leukemia , dna , biochemistry , genetics
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‐γ 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. © 1996 Wiley‐Liss, Inc.