POSSIBLE MECHANISMS OF STIMULATORY EFFECTS OF MESENCHYMAL STROMAL CELLS UPON T CELL RECOVERY DURING CHEMOTHERAPY-INDUCED LYMPHOPENIA

Abstract

The aim of present work was to evaluate the effect of mesenchymal stromal cells (MSCs) from lymphoma patients on the in vitro and in vivo homeostatic proliferation of lymphocytes. Our data have demonstratedfor the first time, that MSCs from lymphoma patient are able to enhance the in vitro proliferation of donor and patient mononuclear cells (MNCs) in response to IL-2 or IL-7. This effect was observed within a wide rangeof MSC-to-MNC ratios (1:50-1:2). Lymphocyte reactivity to IL-2 or IL-7 was found to be an important factor determining the stimulatory effect of MSCs. Ex vivo studies in the patients undergoing autologous hematopoietic stem cell transplantation (AHSCT) have shown that the patients co-transplanted with MSCs exhibited higher proportions of proliferating CD8+T cells (especially, memory cells) at the day of engraftment, than before AHSCT, as compared to the patients subjected to standard AHSCT protocols. Moreover, there was no an increase in apoptosis of naive CD4+T cells that was typical for standard AHSCT. These data indicate that the stimulatory effect of MSCs upon T lymphocyte proliferation following chemotherapy-induced lymphopeniaconcerns, mainly, the memory CD8+T cell population, whereas more efficient recovery of naive CD4+T cells is due to anti-apoptotic effects of MSCs.

Keywords

• mesenchymal stromal cells
• il-2
• il-7
• t-lymphocytes
• proliferation