Invariant NKT cells and immunomodulation of GvHD – review of literature and preclinical data

Czech version

Authors: L. Hejretová ^1,2; K. Weberová ^1,3; M. Čedíková ^3,4; D. Lysák ¹; P. Jindra ¹; M. Holubová ^1,3
Authors‘ workplace: Hematologicko-onkologické oddělení, FN Plzeň ¹; Ústav histologie a embryologie, LF UK v Plzni ²; Biomedicínské centrum, LF UK v Plzni ³; Katedra záchranářství, diagnostických oborů a veřejného zdravotnictví, Fakulta zdravotnických studií, Západočeská Univerzita v Plzni ⁴
Published in: Transfuze Hematol. dnes,28, 2022, No. 3, p. 164-172.
Category: Original Papers
doi: https://doi.org/10.48095/cctahd2022prolekare.cz12

Overview

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 optimalization of transplant procedures, there remains a large group of patients who develop life-threatening forms of GvHD, or whose quality of life after transplantation is reduced due to GvHD. The adoptive administration of immunomodulatory cell populations is an innovative approach that could improve the prognosis of these patients. We had previously used mesenchymal stem cells (MSC) in steroid-refractory GvHD (SR-GvHD) in a clinical trial and we are currently verifying the possibility of using invariant NKT lymphocytes (iNKT) in SR-GvHD treatment. iNKT are a cell population that is able to suppress pathological immune responses and the development of GvHD symptoms. At the same time, iNKT are able to promote anti-tumour immunity – the graft versus leukaemia effect (GvL). In a 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. The study showed that it is possible to prepare a pure population of iNKT with sufficient immunomodulatory capacity comparable to MSCs. While iNKT cells appear to be a promising treatment strategy for post-transplant complications, the significant heterogeneity of their subpopulations will require a deeper assessment of iNKT function and optimisation of their production protocols.

Keywords:

mesenchymal stem cells – immunomodulation – graft-versus-host disease – invariant NKT lymphocytes

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