Interleukin-13 inhibits interleukin-2-induced proliferation and protects chronic lymphocytic leukemia B cells from in vitro apoptosis.

Human interleukin-13 (IL-13) acts at different stages of the normal B-cell maturation pathway with a spectrum of biologic activities overlapping those of IL-4. B chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of slow-dividing and long-lived monoclonal B cells, arrested at the intermediate stage of their differentiation. In vitro, B-CLL cells exhibit a spontaneous apoptosis regulated by different cytokines. In this report, we show that IL-13 (10 to 200 ng/mL) acts directly on monoclonal B-CLL cells from 12 patients. (1) IL-13 enhances CD23 expression and induces soluble CD23 secretion by B-CLL cells but does not exhibit a growth factor activity. (2) IL-13 inhibits IL-2 responsiveness of B-CLL cells, activated either with IL-2 alone or through crosslinking of lgs or ligation of CD40 antigen. (3) IL-13 protects B-CLL cells from in vitro spontaneous apoptosis. The effects of IL-13 on neoplasic B cells were slightly less than those of IL-4 and occurred independently of the presence of IL-4. The present observations show that IL-13 may exhibit a negative regulatory effect on neoplasic B cells in contrast with that observed in normal B cells, and suggest that IL-13 could be an important factor in the pathogenesis of CLL by preventing the death of monoclonal B cells. Moreover, B-CLL may be an interesting model to study the regulation of the expression of IL-13 receptor and/or signal transduction pathways.

[1]  You-Wen He,et al.  The IL-2 receptor gamma c chain does not function as a subunit shared by the IL-4 and IL-13 receptors. Implication for the structure of the IL-4 receptor. , 1995, Journal of immunology.

[2]  R. Puri,et al.  Receptor for Interleukin 13 , 1995, The Journal of Biological Chemistry.

[3]  P. Ferrara,et al.  Characterization and Comparison of the Interleukin 13 Receptor with the Interleukin 4 Receptor on Several Cell Types (*) , 1995, The Journal of Biological Chemistry.

[4]  J. Banchereau,et al.  IL-13 has only a subset of IL-4-like activities on B chronic lymphocytic leukaemia cells. , 1994, Immunology.

[5]  W. Sebald,et al.  Design of human interleukin-4 antagonists inhibiting interleukin-4-dependent and interleukin-13-dependent responses in T-cells and B-cells with high efficiency. , 1994, European journal of biochemistry.

[6]  A. Prentice,et al.  Interleukin-5 (IL-5) increases spontaneous apoptosis of B-cell chronic lymphocytic leukemia cells in vitro independently of bcl-2 expression and is inhibited by IL-4. , 1994, Blood.

[7]  J. Banchereau,et al.  Interleukin-13 inhibits the proliferation of normal and leukemic human B-cell precursors. , 1994, Blood.

[8]  S. Gordon,et al.  Interleukin‐13 alters the activation state of murine macrophages in vitro: Comparison with interleukin‐4 and interferon‐γ , 1994, European journal of immunology.

[9]  J. D. de Vries,et al.  IL-13 induces proliferation, Ig isotype switching, and Ig synthesis by immature human fetal B cells. , 1994, Journal of immunology.

[10]  A. Minty,et al.  Interleukin 13 is a B cell stimulating factor , 1994, The Journal of experimental medicine.

[11]  J. Banchereau,et al.  Interleukin 10 induces apoptotic cell death of B-chronic lymphocytic leukemia cells , 1994, The Journal of experimental medicine.

[12]  C. Figdor,et al.  Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. , 1993, Journal of immunology.

[13]  R. de Waal Malefyt,et al.  An interleukin 4 (IL-4) mutant protein inhibits both IL-4 or IL-13- induced human immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: support for a common component shared by IL-4 and IL-13 receptors , 1993, The Journal of experimental medicine.

[14]  I. Maclennan,et al.  Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bcl‐2 induction , 1993, European journal of immunology.

[15]  G. Zurawski,et al.  Receptors for interleukin‐13 and interleukin‐4 are complex and share a novel component that functions in signal transduction. , 1993, The EMBO journal.

[16]  R. de Waal Malefyt,et al.  Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[17]  R. de Waal Malefyt,et al.  Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[18]  D. Campana,et al.  Interferon gamma inhibits apoptotic cell death in B cell chronic lymphocytic leukemia , 1993, The Journal of experimental medicine.

[19]  J. Banchereau,et al.  Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors. , 1992, Blood.

[20]  G. Delespesse,et al.  Interleukin 4 protects chronic lymphocytic leukemic B cells from death by apoptosis and upregulates Bcl-2 expression , 1992, The Journal of experimental medicine.

[21]  S. Fournier,et al.  CD23 antigen regulation and signaling in chronic lymphocytic leukemia. , 1992, The Journal of clinical investigation.

[22]  M. Auffredou,et al.  Differential inhibition of interleukin 2‐ and interleukin 4‐mediated human B cell proliferation by ionomycin: A possible regulatory role for apoptosis , 1991, European journal of immunology.

[23]  I Nicoletti,et al.  A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. , 1991, Journal of immunological methods.

[24]  S. Orrenius,et al.  Induction of DNA fragmentation in chronic B-lymphocytic leukemia cells. , 1991, Journal of immunology.

[25]  P. Debré,et al.  IL-4 inhibits the expression of high affinity IL-2 receptors on monoclonal human B cells. , 1990, Journal of immunology.

[26]  K. Nilsson,et al.  Interleukin 4 strongly augments or inhibits DNA synthesis and differentiation of B‐type chronic lymphocytic leukemia cells depending on the costimulatory activation and progression signals , 1989, European journal of immunology.

[27]  J. H. Pope,et al.  Spontaneous programmed death (apoptosis) of B‐chronic lymphocytic leukaemia cells following their culture in vitro , 1989, British journal of haematology.

[28]  J. Banchereau,et al.  Interleukin 4 inhibits the proliferation but not the differentiation of activated human B cells in response to interleukin 2 , 1988, The Journal of experimental medicine.

[29]  J. Banchereau,et al.  Interleukin 4 counteracts the interleukin 2-induced proliferation of monoclonal B cells , 1988, The Journal of experimental medicine.

[30]  P. Debré,et al.  Positive effects of interferon-alpha on B cell-type chronic lymphocytic leukemia proliferative response. , 1988, Journal of immunology.

[31]  Bayard,et al.  Rapid hypotonic method for flow cytofluorometry of monolayer cell cultures. Some pitfalls in staining and data analysis. , 1978, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[32]  J. Binet,et al.  A clinical staging system for chronic lymphocytic leukemia. Prognostic significance , 1977, Cancer.

[33]  A. Minty,et al.  Function of the interleukin-2 (IL-2) receptor gamma-chain in biologic responses of X-linked severe combined immunodeficient B cells to IL-2, IL-4, IL-13, and IL-15. , 1995, Blood.

[34]  R. Puri,et al.  Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. , 1993, Science.

[35]  T. Chisesi,et al.  Expression and functional role of tumor necrosis factor receptors on leukemic cells from patients with type B chronic lymphoproliferative disorders. , 1993, Blood.

[36]  M. Kaghad,et al.  Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. , 1993, Nature.