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Clinical immunology : the official journal of the Clinical Immunology Society v.183, 2017년, pp.91 - 98   SCI SCIE SCOPUS
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Retinoic acid induction of CD1d expression primes chronic lymphocytic leukemia B cells for killing by CD8+ invariant natural killer T cells

Ghnewa, Yasmeen G. (Department of Immunology, School of Medicine, Trinity translational Medicine Institute, Trinity College Dublin, Ireland ) ; O'Reilly, Vincent P. (Department of Immunology, School of Medicine, Trinity translational Medicine Institute, Trinity College Dublin, Ireland ) ; Vandenberghe, Elisabeth (Department of Haematology, School of Medicine, Trinity translational Medicine Institute, Trinity College Dublin, Ireland ) ; Browne, Paul V. (Department of Haematology, School of Medicine, Trinity translational Medicine Institute, Trinity College Dublin, Ireland ) ; McElligott, Anthony M. (Department of Haematology, School of Medicine, Trinity translational Medicine Institute, Trinity College Dublin, Ireland ) ; Doherty, Derek G. (Department of Immunology, School of Medicine, Trinity translational Medicine Institute, Trinity College Dublin, Ireland ) ;
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    Abstract Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5. Retinoic acid receptor-α (RAR-α) agonists induced CD1d expression by CLL B cells, restoring their ability to present α-GalCer to CD8α + iNKT cells, resulting in cytolytic degranulation. Thus, RAR-α agonists can augment the anti-tumor activities of iNKT cells against CLL cells in vitro . Their inclusion in iNKT cell-based therapies may benefit patients with CLL. Highlights CD1d expression is reduced on B cells from CLL patients. CLL B cells have reduced capacity to present glycolipid antigens to iNKT cells. Retinoic acid induces CD1d expression by CLL B cells. Retinoic acid primes CLL B cells for killing by CD8α + iNKT cells Including retinoic acid in iNKT cell-based therapies may benefit patients with CLL.


  • 주제어

    Chronic lymphocytic leukemia .   Invariant natural killer T cells .   CD1d .   Retinoic acid .   Cytotoxicity.  

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