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CD40/CD40 Ligand Signal Controls Cytotoxic Ability of Natural Killer Cells After Invariant Natural Killer T Cell Stimulation.

H. Fukuda,1 T. Hiai,1 R. Ishii,1 H. Katsumata,1 T. Kanzawa,1 S. Miyairi,1 M. Ikemiyagi,1 Y. Ishii,2 M. Okumi,1 K. Tanabe.1

1Urology, Tokyo Women's Medical University, Tokyo, Japan
2Cluster for Industry Partnerships (CIP), RIKEN IMS-RCAI, Tokyo, Japan

Meeting: 2017 American Transplant Congress

Abstract number: C115

Keywords: Natural killer cells, Tolerance

Session Information

Session Name: Poster Session C: Innate Immunity

Session Type: Poster Session

Date: Monday, May 1, 2017

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall D1

Because iNKT cells have powerful immune-regulatory function, an administration of iNKT cell ligand; α-galactosylceramide (aGC) is one of the potent strategies for induction of transplant tolerance, although accompanied NK cell activation remains an obstacle. We previously reported that an administration of anti-CD40L monoclonal antibodies decreased IFNg production after iNKT cell activation in murine non-myeloabrative bone marrow transplantation model, and prevented hematopoietic cell rejection. The aim of this study is to examine the impact of CD40/CD40L blockade on NK cell activation after iNKT cell stimulation by liposomal formulation of aGC (lipo-aGC). Splenocytes were obtained from the mice that received lipo-aGC with/without anti-CD40L 6 hr before, and were stained cell surface and intracelluer markers to analyze activation of CD49b+NK cells. The mice stimulated with lipo-aGC showed up-regulation of CD69 and Sca-1, and down-regulation of KLRG-1 on NK cells. They also showed increase in the production of IFNg and granzyme B in NK cells. Anti-CD40L administration did not affect on the expression levels of cell surface markers, whereas it attenuated the production of IFNg and granzyme B, indicating that CD40/CD40L blockade is needed to preclude NK cell cytotoxic reactions. When deleted NK cells with anti-asialoGM1, iNKT cell activation resulted in hematopoietic engraftment without CD40/CD40L blockade. The data collectively suggest that immune-direction after iNKT cell stimulation is controllable by manipulating NK cells with CD40/CD40L signal.

CITATION INFORMATION: Fukuda H, Hiai T, Ishii R, Katsumata H, Kanzawa T, Miyairi S, Ikemiyagi M, Ishii Y, Okumi M, Tanabe K. CD40/CD40 Ligand Signal Controls Cytotoxic Ability of Natural Killer Cells After Invariant Natural Killer T Cell Stimulation. Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Fukuda H, Hiai T, Ishii R, Katsumata H, Kanzawa T, Miyairi S, Ikemiyagi M, Ishii Y, Okumi M, Tanabe K. CD40/CD40 Ligand Signal Controls Cytotoxic Ability of Natural Killer Cells After Invariant Natural Killer T Cell Stimulation. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/cd40cd40-ligand-signal-controls-cytotoxic-ability-of-natural-killer-cells-after-invariant-natural-killer-t-cell-stimulation/. Accessed May 28, 2025.

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