Invariant NKT cells and immunomodulation of graft-versus-host disease – literature review and preclinical data

Abstract

Graft versus host disease (GvHD) is one of the most serious complications of allogeneic hematopoietic stem cell transplantation. Although GvHD mortality is steadily declining due to the optimization of transplantation procedures, there is still a large group of patients who develop a life-threatening form of GvHD or whose GvHD reduces the quality of life after transplantation. Therefore, we focus on finding new treatment modalities that minimize the impact of GvHD on patients. In addition to a number of standard procedures that involve a combination of immunosuppressants, there is a range of other more or less experimental procedures for the prevention and treatment of GvHD. In a clinical study, we administered mesenchymal stem cell (MSC) products in the treatment of steroid-refractory GvHD (SR-GvHD). Also, we investigated the in vitro immunomodulatory potential of other cell populations, especially invariant NKT lymphocytes (iNKT). iNKT are able to suppress the immune response and to prevent development of GvHD together with promoting anti-tumor immunity –  the graft versus leukemia (GvL). In preclinical study, we compared several batches of cultured and expanded iNKT and MSCs from different donors in terms of their immunophenotype and immunomodulatory potential. We quantified the expression of the activation marker CD25 on non-specifically stimulated mononuclear cells after co-cultivation with MSC or iNKT by flow cytometry. We have proven that there are no significant differences in the immunomodulatory potential between MSCs and iNKT. Both cell populations are able to comparably modulate immune responses in vitro. In addition, invariant NKT lymphocytes should simultaneously support the GvL effect.