ctla-4 engagement inhibits th2 but not th1 cell polarisationctla-4接触抑制th2但不是th1细胞分化.pdfVIP

Clinical Developmental Immunology, March 2003, Vol. 10 (1), pp. 13–17 CTLA-4 Engagement Inhibits Th2 but not Th1 Cell Polarisation a b a a b, VANESSA UBALDI , LUCIA GATTA , LUIGIA PACE , GINO DORIA and CLAUDIO PIOLI * aDepartment of Biology, University of Tor Vergata, I-00133, Rome, Italy; bSection of Toxicology and Biomedicine, ENEA C.R. Casaccia, Via Anguillarese 301, I-00060, Rome, Italy 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 ¨ þ cell subset differentiation. Naıve 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-g- 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 ¨ þ engagement during differentiation inhibits polarisation of naıve CD4 cells to the Th2 but not the Th1 cell subset. At variance