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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