Fas/FasL interaction mediates imbalanced cytokine/cytotoxicity responses of iNKT cells against Jurkat cells. (July 2018)

• Record Type: Journal Article
• Authors: Dou, Rui; Hong, Zhenya; Tan, Xiaosheng; Hu, Fenfen; Ding, Yajie; Wang, Wei; Liang, Zhihui; Zhong, Rongrong; Wu, Xiongwen; Weng, Xiufang
• Is Part Of: Molecular immunology. Volume 99(2018:Jul.)
• Page Start: 145
• Page End: 153
• Publication Date: 2018-07
• Subjects: iNKT invariant natural killer T -- FasL Fas ligand -- α-GalCer α-galactosylceramide -- APC antigen presenting cells; CD1d level -- Malignant T cell lines -- Impaired cytokine production -- Intensive cytotoxicity -- iNKT cell responses; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2018.05.011
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: iNKT cells exhibited imbalanced cytokine/cytotoxicity responses against Jurkat cells. The imbalanced iNKT cell responses were CD1d dependent and relied mostly on Fas/FasL interaction. Elevated CD1d levels and defects of iNKT cells were found in T-cell lymphoma patients. Exogenous IL-2 helped to overcome the defects of iNKT cells from T lymphoma patients. Abstract: The rapid antitumor cytokine production and direct cytotoxicity confer invariant NKT (iNKT) cells ideal candidates for cancer therapy. However, the therapeutic potential of iNKT cells in T-cell malignant diseases remains elusive, as antigen presentation by T cells (T-T presentation) has been suggested to induce hyporesponsiveness of iNKT cells. In this study, we found discrepancies in iNKT cell responses against two T cell-origin cell lines (Jurkat and Molt-4). Human iNKT cells exhibited more intensive cytotoxicity and less efficient cytokine production in response to Fas-bearing Jurkat cells than those to the Fas-negative tumor cells (Molt-4 and myeloid-derived K562). The imbalanced cytokine/cytotoxicity responses of iNKT cells against Jurkat cells were CD1d-dependent and relied mostly on Fas/FasL interaction. The impairment in cytokine production could be overcome by Fas/FasL blocking antibodies and exogenous IL-2. Elevated CD1d levels as well as CD1d and Fas co-localization were found in T-cell lymphomas. However, defects in frequency and function of circulating iNKT cells were observed in the patients, which could be partly rescued by exogenous IL-2. Collectively, the Fas/FasL-dependent aberrant iNKT cell responses and the reversibility of the defects suggest the distinct iNKT cell manipulation in CD1d- and Fas-bearing T cell malignancies.