Interleukin-11 induces proliferation of human T-cells and its activity is associated with downregulation of p27(kip1)
A Curti, A Tafuri, MR Ricciardi, P Tazzari, MT Petrucci, M Fogli, M Ratta, R Lapalombella, E Ferri, S Tura, M Baccarani, RM Lemoli

Author Affiliations

  1. A Curti,
  2. A Tafuri,
  3. MR Ricciardi,
  4. P Tazzari,
  5. MT Petrucci,
  6. M Fogli,
  7. M Ratta,
  8. R Lapalombella,
  9. E Ferri,
  10. S Tura,
  11. M Baccarani and
  12. RM Lemoli
  1. Institute of Hematology and Medical Oncology Lorenzo & Ariosto Seragnoli , University of Bologna, Bologna, Italy.


BACKGROUND AND OBJECTIVES: We have recently shown that interleukin (IL-)11 induces polarization of human T-cells by inhibiting macrophage production of IL-12 and by exerting a direct effect on CD4+ T-cells. In this study, we investigated the effects of IL-11 on the kinetic activation and apoptosis of T-cell subsets stimulated with anti-CD3/CD28 antibodies, anti-CD3 and IL-2 or dendritic cells. DESIGN AND METHODS: Apoptosis and cell cycle analysis of T-cells were assessed by double staining with propidium iodide and intracellular Ki-67 and by acridine orange staining. The expression of the negative regulator of the cell cycle p27Kip1 (p27) was also determined by flow cytometry. RESULTS: Our results show that 18 hours of incubation with IL-11 resulted in a significantly higher number of cycling CD4+ cells, CD4+CD45RA+ naive T-cells and CD4+CD45RO+ memory T-cells, but not of CD8+ cells. The kinetic activity of IL-11 was observed up to 72 hours, when the peak value of S-phase cells occurred. IL-11 also significantly enhanced CD4+ and CD4+CD45RA+ cell proliferation when T-cells were co-incubated with allogeneic dendritic cells. Conversely, IL-11 did not protect any of the T-cell subsets from apoptosis. At the functional level, a type-2 cytokine pattern of cultured T-lymphocytes was observed after 5 days of incubation with IL-11. Proliferation and functional activation of T-cells were preceeded by downregulation of p27, which occurred as early as 12 hours after incubation with IL-11. INTERPRETATION AND CONCLUSIONS: IL-11 induces Th-2 polarization and cell-cycle entry of human CD4+, CD4+CD45RA+ and CD4+CD45RO+cells and their activation is associated with the downregulation of p27.