Interleukin-11 induces proliferation of human T-cells and its activity is associated with downregulation of p27(kip1).
OBJECTIVE
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.


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.


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.
Curti
Antonio
A
Institute of Hematology and Medical Oncology Lorenzo & Ariosto Seràgnoli , University of Bologna, Bologna, Italy.
Tafuri
Agostino
A
Ricciardi
Maria R
MR
Tazzari
Pierluigi
P
Petrucci
Maria T
MT
Fogli
Miriam
M
Ratta
Marina
M
Lapalombella
Rosa
R
Ferri
Elisa
E
Tura
Sante
S
Baccarani
Michele
M
Lemoli
Roberto M
RM
D017209:Apoptosis / Q000187:drug effects; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015536:Down-Regulation; D006801:Humans; D017370:Interleukin-11 / Q000494:pharmacology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000187:drug effects; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects*
C436291:CDKN1B protein, human; D002352:Carrier Proteins; D017370:Interleukin-11; D047908:Intracellular Signaling Peptides and Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27