Research Scientist Ann & Lurie Children's Hospital / Northwestern University Chicago, Illinois, United States
Disclosure(s):
Hee Kang, PhD: No financial relationships to disclose
Introduction/Rationale: In prenatal allotransplantation (Balb/c to C57BL/6), NK cells play a critical role in engraftment or rejection of graft in recipients. Adoptively transferred naïve hostile (Ly49D-AFG+) NK cells were converted into friendly phenotype (Ly49D+AFG+) in tolerant engrafter chimera mice. Therefore, we hypothesized that hostile NK cells can be converted into tolerant NK cells in tolerogenic (abundant TGF-b1) environment.
Methods: To test this hypothesis, isolated naïve hostile NK cells were cultured with allogeneic target cells in the presence e of high dose (1ng/ml) TGF-b1 or anti-CD48 antibody that stimulate NK cells to produce TGF-b. A week later, we analyzed the frequencies of activating NK cell receptor (Ly49D) and inhibiting receptor (Ly49A, F, and G) in hostile NK cell population.
Results: We found that hostile NK cells cultured with anti-CD48 and allogeneic target cells, expressed inhibitory receptor (Ly49AFG+) but decreased the frequency of activating receptor, Ly49D in hNK cell population. High dose TGF-b1 can convert hostile NK cells to friendly NK cells no matter with or without allo stimulation.
Conclusion: These results prove that NK cell tolerance can arise from down-regulation of activating receptor and/or expressing inhibitory receptors upon stimulation with allogeneic target cells in tolerogenic environment (presence of TGF-b1). It provides a possible tolerance therapy to protect graft in rejecting recipient following prenatal allo transplantaion.
