Introduction
The immune system undergoes a series of physiological functional declines with ageing, which are termed immunosenescence and partly result in poor responses to vaccines and increased incidence of severe infectious diseases and cancer in the elderly population[1, 2]. Some studies have shown that the adaptive immune system, especially T cells, is more susceptible to ageing than the innate immune system[3, 4]. Our and other previous studies showed decreased frequencies of bone marrow (BM) lymphoid progenitor cells and naïve T cells but increased frequencies of memory T cells, as well as unbalanced effector T cell subset differentiation, such as increased T helper (Th)-1 and T cytotoxic (Tc)-1 cells, in elderly individuals[1, 2, 5]. Emerging evidence has indicated that decreased BM lymphoid progenitor cells and involution of the thymus may be responsible for the alterations in T cell subsets with ageing[6-8]. However, the underlying mechanism of the more balanced differentiation of effector T cell subsets in young individuals than in elderly individuals remains to be clarified.
The BM, as both a primary and secondary lymphoid organ, plays an essential role in regulating the development and differentiation of T cells[9]. Endothelial cells (ECs), which line the interior of blood and lymphatic vessels, are instructive components of the BM microenvironment[10]. In addition to supporting self-renewal and lineage-specific differentiation of haematopoietic stem cells through the release of specific angiocrine factors[11-13], ECs also play crucial immunological roles, particularly in T cell recruitment and activation[14, 15]. Emerging evidence has suggested that ECs exhibit a semi-professional antigen-presenting cell phenotype by expressing classic innate immune receptors such as Toll-like receptors (TLRs), NOD-like receptors, and inducible costimulatory ligands[16-18]. Although controversial, some studies have suggested that ECs express costimulatory molecules such as CD80 and CD86[19, 20]. Activation of EC TLRs by lipopolysaccharide (LPS) or lipopeptide upregulated the secretion of specific cytokines, chemokines and adhesion molecules and increased the recruitment and activation of T cells[14, 15]. In addition, recent studies demonstrated that ECs were able to suppress T cell proliferation and modulate T cells to produce fewer proinflammatory cytokines through tumour necrosis factor and its receptor 2 signalling pathway[10]. Moreover, liver sinusoidal ECs have been shown to modulate naïve CD8+ T cells to secrete less interferon-γ (IFN-γ) and interleukin (IL)-2 by cross-presentation to CD8+ T cells, which then induces immune tolerance[21, 22]. However, whether the frequency and functions of BM ECs, especially their capacity to regulate effector T cell subsets, differ between young and old individuals remains to be clarified.
Therefore, the current study was performed to evaluate the frequency and reactive oxygen species (ROS) levels of BM ECs among young, middle-aged, and old healthy individuals. Moreover, we investigated whether the function of BM ECs, especially their capacity to modulate the differentiation of effector T cell subsets, differs between young and old individuals and the underlying mechanism of this immunomodulatory discrepancy. Our study may contribute to improving the understanding of T cell subset alterations with ageing.