title: Activation of human T cell lymphotropic virus type I-infected T cells is independent of B7 costimulation.
abstract: Two distinct signals are required to activate T cells: an Ag-specific signal and a costimulatory signal mediated primarily by B7-1 (CD80) and B7-2 (CD86) through interactions with CD28. Costimulation appears to be critical in regulating autoreactive T cell responses. Here, we demonstrate that, in contrast to the parental uninfected T cell clone, a T cell clone infected by human T cell lymphotropic virus type I (HTLV-I) displays a remarkably enhanced response to Ag in the absence of B7 costimulation. Chinese hamster ovary cells either transfected with DRB1*1501 (t-DR2) alone or cotransfected with DR2 and either B7-1 or B7-2 were fixed, pulsed with myelin basic protein peptide 84-102 (MBPp84-102), and used as APCs. The MBPp84-102-reactive T cell clone Ob1A12.8 required costimulation with either B7-1 or B7-2 molecules, as the response to Ag was reduced by 90% in the absence of B7 costimulation. However, this requirement for B7 costimulation was abrogated after productive infection by HTLV-I. Stimulation of HTLV-I-infected T cells by MBPp84-102/t-DR2 induced the secretion of IL-5 and IFN-gamma, which approached the level induced in the presence of B7 costimulation, whereas IL-4 was induced to one third of its maximal level. Consistently, the secretion of IL-5 and IFN-gamma was not significantly inhibited by anti-B7-1 and B7-2 Abs, whereas IL-4 was inhibited by approximately 50%. In contrast, uninfected T cells required either B7-1 or B7-2 costimulation for significant cytokine secretion, and this response was inhibited by anti-B7-1 and B7-2 Abs. These findings suggest that HTLV-I-infected autoreactive T cells have the potential to induce an autoimmune response in the absence of B7 expression in the target organ. This may be of particular interest in the elucidation of HTLV-I pathogenicity given the association of HTLV-I infection with autoimmune-like diseases.
authors.affiliation: Laboratory of Molecular Immunology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: C
authors.initials: C
authors.lastname: Scholz
authors.forename: G J
authors.initials: GJ
authors.lastname: Freeman
authors.forename: E A
authors.initials: EA
authors.lastname: Greenfield
authors.forename: D A
authors.initials: DA
authors.lastname: Hafler
authors.forename: P
authors.initials: P
authors.lastname: Höllsberg
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015551:Autoimmunity / Q000502:physiology*; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology*; D051940:B7-2 Antigen; D001483:Base Sequence; D018106:CD28 Antigens / Q000276:immunology; D016466:CHO Cells / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D053616:Janus Kinase 3; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D018106:CD28 Antigens; C497964:CD86 protein, human; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D004676:Myelin Basic Protein; D015847:Interleukin-4; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507933:JAK3 protein, human; D053616:Janus Kinase 3