Impact of different mesenchymal stromal cell types on T-cell activation, proliferation and migration

Abstract

Mesenchymal stromal cells (MSCs) isolated from different tissue sources may present distinct immunomodulatory profiles. As lymphocyte responses are a combination of several distinct steps, we evaluated and compared the impact of MSCs from different sources on the activation, proliferation and migration of T-cells. We demonstrated that tissue-derived MSCs have important immunomodulatory effects. AT-MSCs induced potent anti-proliferative and anti-inflammatory (IFN-γ downregulation) effects and differentially modulated several T-cell activation markers (CD23, CD26, CD45, and CD69). Among all the MSC types tested, only AT-MSCs induced significant downregulation of CD26 and CD45 expression. Of importance, AT-MSCs maintained a sustained expression of CD69. AT-MSCs, particularly following exposure to an inflammatory environment, promoted the migration of lymphocytes into their surrounding environment. The AT-MSCs may increase recruitment of T lymphocytes by upregulation of IL-8 and CCL5 secretion. Following their migration, T-cells interact with MSCs, which can impair lymphocyte proliferation and activation depending on their origin. Inflammatory T-cells appeared to be progressively suppressed, which may lead to a population of lymphocytes with a regulatory phenotype. These findings are relevant, as they increase our understanding of the different immunomodulatory effect of MSCs as well as their behavior in an inflammatory environment.