The combination of IKK? inhibitor and everolimus modulates expression of IL-10 in HTLV-1-infected T cells.

The combination of IKK? inhibitor and everolimus modulates expression of IL-10 in HTLV-1-infected T cells.

Immunology. 2012 Dec 27;

Authors: Nishioka C, Ikezoe T, Yang J, Udaka K, Yokoyama A

Abstract
Adult T-cell leukemia-lymphoma (ATLL) is an aggressive malignancy of CD4(+) /CD25(+) T lymphocytes, and characterized with severely compromised immunosystem in which the human T-cell lymphotropic virus type 1 (HTLV-1) has been recognized as the etiologic agent. This study found that an I?B kinase ? (IKK?) inhibitor Bay11-7082 inactivated mammalian target of rapamycin (mTOR), signal transducer and activator of transcription 3 (STAT3), and transcription factor nuclear factor-?B (NF-?B) in HTLV-1-infected T cells, which was significantly enhanced in the presence of an mTOR inhibitor everolimus. In addition, Bay11-7082 decreased production of immunosuppressive cytokine interleukin-10 (IL-10), which was further downregulated when Bay11-7082 was combined with evelolimus in HTLV-I-infected T and ATLL cells isolated from patients. IL-10 is known to inhibit maturation and the antigen-presenting function of dendritic cells (DCs). The culture media of HTLV-I-infected MT-1 cells which contained a great amout of IL-10 hampered TNF-?-induced maturation of DCs isolated from healthy volunteers. Notably, culture supernatant of MT-1 cells treated by the combination of Bay11-7082 and everolimus augmented maturation of DCs in association with a decrease in production of IL-10 and enhanced the allostimulatory function of DCs. Similarly, when DCs isolated from ATLL patients were treated with the combination of Bay11-7082 and everolimus, they were fully maturated and their capability to stimulate proliferation of lymphocytes was augmented. Taken together, the combination of Bay11-7082 and everolimus might exhibit immunostimulatory properties in HTLV-1-infected T and ATLL cells isolated from patients, and this combination may be potentially therapeutic to regain the compromised immunosystem in ATLL patients. � 2012 The Authors. Immunology � 2012 Blackwell Publishing Ltd.

PMID: 23278479 [PubMed - as supplied by publisher]

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