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CTLA-4 engagement inhibits Th2 but not Th1 cell polarisation

TitoloCTLA-4 engagement inhibits Th2 but not Th1 cell polarisation
Tipo di pubblicazioneArticolo su Rivista peer-reviewed
Anno di Pubblicazione2003
AutoriUbaldi, V., Gatta L., Pace L., Doria G., and Pioli Claudio
RivistaClinical and Developmental Immunology
Volume10
Paginazione13-17
ISSN17402522
Parole chiaveanimal cell, Animals, Antibodies, Antigens, article, CD, CD4-Positive T-Lymphocytes, cell differentiation, Cell Polarity, Cells, Cultured, cytokine production, Cytokines, cytotoxic T lymphocyte antigen 4, Differentiation, effector cell, enzyme linked immunosorbent assay, Enzyme-Linked Immunosorbent Assay, Flow cytometry, fluorescence activated cell sorting, gamma interferon, Inbred C57BL, Interferon Type II, interleukin 12, interleukin 4, Interleukins, lymphocyte activation, lymphocyte differentiation, lymphoproliferative disease, Mice, Monoclonal, Monoclonal antibody, monoclonal antibody cd28, monoclonal antibody CD3, mouse, nonhuman, Phenotype, priority journal, Reverse Transcriptase Polymerase Chain Reaction, RNA, signal transduction, supernatant, Th1 cell, Th1 Cells, Th2 cell, Th2 Cells, unclassified drug
Abstract

CTLA-4 deficient mice show severe lymphoproliferative disorders with T helper sub-population skewed toward the Th2 phenotype. In the present work, we investigated the role of CTLA-4 in T helper cell subset differentiation. Naïve CD4+ cells were stimulated with anti-CD3 and anti-CD28 mAbs in the presence of either IL-12 of IL-4 to induce polarisation to Th1 or Th2 cells, respectively. Under these two polarising conditions cells express comparable levels of CTLA-4. CTLA-4 was stimulated by plastic-bound mAb. The frequency of IFN-γ- and IL-4-producing cells were estimated by FACS analysis. In parallel cultures, polarised Th1 and Th2 cells were re-stimulated with anti-CD3 and anti-CD28 mAbs for 48 h and their culture supernatants analysed by ELISA. Results show that CTLA-4 engagement during differentiation inhibits polarisation of naïve CD4+ cells to the Th2 but not the Th1 cell subset. At variance, once cells are polarised, CTLA-4 engagement inhibits cytokine production in both effector Th2 and Th1 cells. Altogether these data indicate that CTLA-4 may interfere not only in the signalling involved in acute transcriptional activation of both Th1 and Th2 cells but also in the development of one of the Th cell subsets.

Note

cited By 18

URLhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-0141925700&doi=10.1080%2f10446670310001598519&partnerID=40&md5=b3ab50abbf18653586b39abab526f46a
DOI10.1080/10446670310001598519
Citation KeyUbaldi200313