CTLA-4 engagement inhibits Th2 but not Th1 cell polarisation.
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. CTLA4 was stimulated by plastic-bound mAb. The frequency of IFN-gamma- 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 naive 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.
Department of Biology, University of Tor Vergata, 1-00133, Rome, Italy.
Vanessa
V
Ubaldi
Lucia
L
Gatta
Luigia
L
Pace
Gino
G
Doria
Claudio
C
Pioli
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007378:Interleukins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012313:RNA / Q000302:isolation & purification; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D016207:Cytokines; D007378:Interleukins; D012313:RNA; D007371:Interferon-gamma