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CTLA-4 regulates allergen response by modulating GATA-3 protein level per cell

TitleCTLA-4 regulates allergen response by modulating GATA-3 protein level per cell
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2007
AuthorsNasta, F., Corinti S., Bonura A., Colombo P., Di Felice G., and Pioli Claudio
Keywordsallergen, Allergens, animal cell, animal experiment, Animals, Antibodies, Antigens, article, CD, cell differentiation, Cells, controlled study, Cultured, cytotoxic T lymphocyte antigen 4, Differentiation, Female, gamma interferon, GATA3 Transcription Factor, gene expression regulation, immune response, immunization, immunoglobulin blood level, Immunoglobulin E, immunoglobulin G, immunoglobulin G2a, immunoglobulin producing cell, Immunomodulation, in vivo study, Inbred BALB C, interleukin 4, interleukin 5, Interleukin-4, Messenger, messenger RNA, Mice, Monoclonal, Monoclonal antibody, mouse, nonhuman, Parietaria, Plant Proteins, pollen antigen, priority journal, protein expression, Recombinant Proteins, RNA, Th1 cell, Th2 cell, Th2 Cells, transcription factor GATA 3, transcription factor T bet

T helper type 2 (Th2) cell differentiation requires the expression of GATA-3, a transcription factor that allows transcriptional activation of Th2 cytokine genes through chromatin remodelling. We investigated the role of the negative costimulatory receptor cytotoxic T-lymphocyte antigen 4 (CTLA-4) in the regulation of GATA-3 expression, Th2 differentiation and immunoglobulin production during the immune response to allergens. BALB/c mice were immunized with a recombinant major allergenic component of Parietaria judaica pollen, rPar j I, and treated with blocking anti-CTLA-4 or control antibodies. Results showed that in vivo CTLA-4 blockade enhanced the Par j I-specific immunoglobulin E (IgE) serum level. In contrast, Par j I-specific IgG2a serum level was reduced, suggesting that CTLA-4 blockade skewed immunoglobulin production towards interleukin-4 (IL-4) -dependent immunoglobulin isotypes. Consistently, CTLA-4 blockade increased the frequency of Par j I-specific Th2 cells but not Th1 cells, as well as IL-4 and IL-5 but not interferon-γ production. Our data also showed that CTLA-4 blockade enhanced the GATA-3:T-bet messenger RNA ratio. Interestingly, in vivo CTLA-4 blockade did not increase the frequency of GATA-3 protein-expressing cells. In contrast, it enhances GATA-3 protein level per cell. Further, in vitro results show that the anti-CTLA-4 monoclonal antibody, by competing with CD80 for CTLA-4 binding, induced an enhancement in the frequency of IL-4-producing cells that correlates with the increase in GATA-3 protein level per cell. In conclusion, CTLA-4, by affecting the level of GATA-3 per cell, contributes to keeping this factor under the threshold required to become a Th2 effector cell. Consequently, it affects IgE/IgG2a production and contributes to the outcome of allergen-specific immune responses. © 2007 Blackwell Publishing Ltd.


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Citation KeyNasta200762