"VSports app下载" Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official. Federal government websites often end in . gov or VSports app下载. mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

Review
. 2017 Jul 31:8:900.
doi: 10.3389/fimmu.2017.00900. eCollection 2017.

Invariant Natural Killer T Cells As Suppressors of Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation

Affiliations
Review

Invariant Natural Killer T Cells As Suppressors of Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation

Melissa Mavers et al. Front Immunol. .

Abstract

Invariant natural killer T (iNKT) cells serve as a bridge between innate and adaptive immunity and have been shown to play an important role in immune regulation, defense against pathogens, and cancer immunity VSports手机版. Recent data also suggest that this compartment of the immune system plays a significant role in reducing graft-versus-host disease (GVHD) in the setting of allogeneic hematopoietic stem cell transplantation. Murine studies have shown that boosting iNKT numbers through certain conditioning regimens or adoptive transfer leads to suppression of acute or chronic GVHD. Preclinical work reveals that iNKT cells exert their suppressive function by expanding regulatory T cells in vivo, though the exact mechanism by which this occurs has yet to be fully elucidated. Human studies have demonstrated that a higher number of iNKT cells in the graft or in the peripheral blood of the recipient post-transplantation are associated with a reduction in GVHD risk, importantly without a loss of graft-versus-tumor effect. In two separate analyses of many immune cell subsets in allogeneic grafts, iNKT cell dose was the only parameter associated with a significant improvement in GVHD or in GVHD-free progression-free survival. Failure to reconstitute iNKT cells following allogeneic transplantation has also been associated with an increased risk of relapse. These data demonstrate that iNKT cells hold promise for future clinical application in the prevention of GVHD in allogeneic stem cell transplantation and warrant further study of the immunoregulatory functions of iNKT cells in this setting. .

Keywords: allogeneic hematopoietic stem cell transplantation; graft-versus-host disease; graft-versus-tumor effect; invariant natural killer T cells; regulatory T cells. V体育安卓版.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Roles of invariant natural killer T cells in allogeneic stem cell transplantation. Depicted are the variety of roles for iNKT in allogeneic stem cell transplantation which have been demonstrated in multiple studies, including graft-versus-tumor effect, antimicrobial effect, and suppression of graft-versus-host disease (GVHD). Purported mechanisms by which iNKT may function to suppress GVHD are shown. Red color represents inflammatory phenotype, blue color represents suppressive or anti-inflammatory phenotype, orange circle represents endogenous lipid antigen, foreign lipid antigen, or exogenous synthetic lipid antigen [i.e., alpha-galactosylceramide (α-GalCer)]. iNKT, invariant natural killer T cells; TCR, T cell receptor; DC, dendritic cell; IL, interleukin; TGF, transforming growth factor; MDSC, myeloid-derived suppressor cell; Treg, regulatory T cell; T, T lymphocyte.

References

    1. Magenau J, Reddy P. Next generation treatment of acute graft-versus-host disease. Leukemia (2014) 28(12):2283–91.10.1038/leu.2014.195 - DOI - PubMed
    1. Ferrara JLM, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet (2009) 373(9674):1550–61.10.1016/S0140-6736(09)60237-3 - "V体育ios版" DOI - PMC - PubMed
    1. Lantz O, Bendelac A. An invariant T cell receptor alpha chain is used by a unique subset of major histocompatibility complex class I-specific CD4+ and CD4-8- T cells in mice and humans. J Exp Med (1994) 180(3):1097–106.10.1084/jem.180.3.1097 - DOI - PMC - PubMed
    1. Bendelac A, Savage PB, Teyton L. The biology of NKT cells. Annu Rev Immunol (2007) 25:297–336.10.1146/annurev.immunol.25.022106.141711 - DOI - PubMed
    1. Brennan PJ, Brigl M, Brenner MB. Invariant natural killer T cells: an innate activation scheme linked to diverse effector functions. Nat Rev Immunol (2013) 13(2):101–17.10.1038/nri3369 - DOI - PubMed