Location of Repository

CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation

By Vanessa Ubaldi, Lucia Gatta, Luigia Pace, Gino Doria and Claudio Pioli


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 or 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

Topics: Research Article
Publisher: Hindawi Publishing Corporation
OAI identifier: oai:pubmedcentral.nih.gov:2270672
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://www.pubmedcentral.nih.g... (external link)
  • Suggested articles



    1. (1995). Antigen-dependent clonal expansionofatracepopulationofantigen-specificCD4Tcellsinvivo is dependent on CD28 costimulation and inhibited by CTLA-4”,
    2. (1997). CD28 costimulation promotes the production of Th2 cytokines”,
    3. (1996). CD28-deficient mice generate an impaired Th2 response to Schistosoma mansoni infection”,
    4. (1995). Critical role of CD28/B7 costimulation in the development of human
    5. (1996). CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis”,
    6. (1996). CTLA-4 engagement inhibits IL-2 accumulation and cell cycle progression upon activation of resting T cells”,
    7. (1996). CTLA-4 ligation blocks CD28-dependent T cell activation”,
    8. (1999). CTLA-4-mediated inhibition of early events of T cell proliferation”,
    9. (1996). CTLA-4: a negative regulator of autoimmune disease”,
    10. (1998). Cytokines induce the development of functionally heterogeneous T helper cell subsets”,
    11. (1999). Cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibits CD28-induced IkBa degradation and RelA activation”,
    12. (1996). Enhancement of antitumor immunity by CTLA-4 blockade”,
    13. (1996). Functional diversity of helper T lymphocyte”,
    14. (1995). Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4”,
    15. (1999). Lymphoproliferative disorder in CTLA-4 knockout mice is characterized by CD28-regulated activation of Th2 responses”,
    16. (1995). Lymphoproliferative disorders with early lethality in mice deficient
    17. (1998). Molecular basis of T cell inactivation by CTLA-4”,
    18. (1997). responses: the alternative approaches”,
    19. (1998). Role of mRNA stability in the different patterns of cytokine production by CD4 cells from young and old mice”,
    20. (2001). T-cell regulation by CD28 and CTLA-4”,

    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.