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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2758-2763
IMMUNOBIOLOGY
Interleukin-11 induces Th2 polarization of human
CD4+ T cells
Antonio Curti,
Marina Ratta,
Silvia Corinti,
Giampiero Girolomoni,
Francesca Ricci,
Pierluigi Tazzari,
Michela Siena,
Alexis Grande,
Miriam Fogli,
Sante Tura, and
Roberto M. Lemoli
From the Institute of Hematology and Medical Oncology
"L. e A. Seràgnoli," University of Bologna, Bologna, Italy;
Immunohematology Service, Sant'Orsola Hospital, Bologna, Italy;
Istituto Dermopatico dell' Immacolata IRCCS, Rome, Italy; and
Institute of Biological Chemistry, University of Modena, Modena, Italy.
Exploration of the immunomodulatory activities of the
multifunctional cytokine interleukin-11 (IL-11) has prompted several therapeutic applications. The immunomodulatory effects of IL-11 on
human antigen-presenting cells and on T cells were investigated. IL-11
inhibited IL-12 production by activated CD14+ monocytes,
but not by mature dendritic cells (DCs) stimulated via CD40 ligation.
Moreover, IL-11 did not affect either DC maturation, as demonstrated by
phenotypic analysis and evaluation of cytokine production, or DC
generation from progenitor cells in the presence of specific growth
factors. Molecular analysis demonstrated the expression of IL-11
receptor messenger RNA in highly purified CD14+ monocytes,
CD19+ B cells, CD8+, and CD4+
T cells, and CD4+CD45RA+ naive T
lymphocytes. In keeping with this finding, IL-11 directly prevented Th1
polarization of highly purified CD4+CD45RA+
naive T cells stimulated with anti-CD3/CD28 antibodies, as demonstrated by significant increases of IL-4 and IL-5, by significantly decreased interferon- production and by flow cytometry intracellular staining of cytokines. Coincubation of naive T cells with DCs, the most potent
stimulators of Th1 differentiation, did not revert IL-11-mediated Th2
polarization. Furthermore, parallel experiments demonstrated that the
activity of IL-11 was comparable with that induced by IL-4, the most
effective Th2-polarizing cytokine. Taken together, these findings show
that IL-11 inhibits Th1 polarization by exerting a direct effect on
human T lymphocytes and by reducing IL-12 production by macrophages.
Conversely, IL-11 does not exert any activity on DCs. This suggests
that IL-11 could have therapeutic potential for diseases where Th1
responses play a dominant pathogenic role.
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