Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation

Abstract

Human MSC fail to stimulate allogeneic PBMC or T-cell proliferation in mixed cell cultures. Unlike other nonprofessional APC, this failure of function is not reversed by provision of CD28-mediated costimulation nor gamma-interferon pretreatment. Rather, MSC actively inhibit T-cell proliferation, suggesting that allogeneic MSC transplantation might be accomplished without the need for significant host immunosuppression.

Immunoregulatory function of mesenchymal stem cells

“…On steady state, MSC constitutively express low surface densities of MHC class I molecules and are negative for MHC class II as well as for costimulatory molecules such as CD80, CD86 and CD40. Both MHC class I and II molecules are up-regulated by inflammatory stimuli [14,25,26]. In addition, MSC express different adhesion molecules including several integrins [27].…”

“…The MSC capacity of inducing proliferative responses by allogeneic PBMC represents a controversial issue [14,25,26,28]; notably, however, both human and murine MSC are generally considered to be poorly immunogenic cells. MSC can also produce a variety of growth factors, cytokines, chemokines and proteases that are likely to play a role either in their immunomodulatory or in their migratory function [29][30][31].…”

“…Inhibition of T cell proliferation resulted in the decreased production of effector Th1 cytokines [16,42,46]; however, the expression of activation markers in T cells that have been cultured with MSC remains a controversial issue [39,43,45,47]. Inhibition of T cell proliferation by MSC appears to be subsequent both to cell-to-cell interaction and to the release of soluble factors, and it is conceivable that discrepant findings reported in the literature reflect differences in the experimental conditions used [13,14,16,48,49]. TGF-b1 and HGF [13], indoleamine 2,3-dioxygenase (IDO) [50] and prostaglandin E2 (PGE-2) [46] represent MSC-derived molecules that have been proposed to exert immunomodulatory activity on T cell responses.…”

“…More recently, MSC have been shown to inhibit T cell proliferation upon antigen stimulation [12][13][14]. Since these early reports, many studies have demonstrated that MSC affect the function of different immunocompetent cell types, lending support to their pioneering utilization in acute graft-versus-host disease (GVHD) [15] and providing the rationale for their possible use in the treatment of autoimmune disorders [16].…”

Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

“…Interestingly, these MSCs have also been shown to have a wider differentiation capability in vitro and in vivo than previously appreciated, at least in some experimental models, [10][11][12] and thus have attracted attention as very desirable cells for regenerative medicine. Furthermore, MSCs from BM and other tissues possess unique immunological characteristics that make them even more attractive for potential clinical applications [13][14][15][16].…”