The mechanism of nasal tolerance in lupus prone mice is T-cell anergy induced by immature B cells that lack B7 expression

• Published in: Journal of autoimmunity 2006-03, Vol.26 (2), p.116-126
• Main Authors: Wu, Henry Yim, Monsonego, Alon, Weiner, Howard L.
• Format: Article
• Language: English
• Subjects: Anergy; Animals; Antibody Formation - immunology; Antigen Presentation - immunology; Antigen-Presenting Cells - immunology; B cell; B-Lymphocytes - immunology; B7-2 Antigen - analysis; B7-2 Antigen - immunology; B7-2 Antigen - metabolism; Biological and medical sciences; CD4-Positive T-Lymphocytes - immunology; Clonal Anergy - immunology; Coculture Techniques; Down-Regulation; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; General aspects; Histone peptide; Histones - chemistry; Histones - immunology; Immunodominant Epitopes - chemistry; Immunodominant Epitopes - immunology; Immunopathology; Leukocyte Common Antigens - analysis; Leukocyte Common Antigens - immunology; Lupus Erythematosus, Systemic - immunology; Lymphocyte Activation; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred NZB; Nasal tolerance; Nose - immunology; T-Lymphocytes - immunology; Th1 Cells - immunology
• ISSN: 0896-8411; 1095-9157
• DOI: 10.1016/j.jaut.2005.11.005

To determine if B cells of lupus prone NZB mice possess intrinsic defects that directly lead or contribute to T-cell hyper-responsiveness, we injected age-, sex- and MHC II-matched NZB and Balb/c mice with histone peptide H471 representing a dominant Th cell epitope in histone H4 of the nucleosome. We found that B220 + B cells of NZB mice express high levels of surface CD86 following antigen priming. We cocultured CD4 + T and B220 + B cells of naïve or peptide primed NZB and Balb/c mice in the presence of peptide. Antigen presentation by autoimmune B cells of NZB mice induced hyper-responsiveness from normal CD4 + T cells of Balb/c mice. T-cell hyper-responsiveness is a result of CD86 costimulation by B cells of NZB mice. Induction of nasal tolerance to H471 in NZB mice suppressed CD86 surface expression and led to downregulation of T-cell proliferative response and cytokine production. More interestingly, B220 + B cells from nasally tolerized NZB mice induced T-cell anergy to anti-CD3 and anti-CD28 antibody stimulation in vitro. The anergic T cells do not possess suppressive function in coculture with naïve responder T cells nor produce suppressive cytokines interleukin 10 and transforming growth factor-beta in vitro.