Characterization and functionality of the CD200-CD200R system during mesenchymal stromal cell interactions with T-lymphocytes.

Mesenchymal stromal cells (MSCs) possess a specific immunological profile that makes them potentially useful for immune-based therapies. Adipose tissue (AT) and Wharton's jelly (WJ) are considered to be valuable alternatives to bone marrow (BM) as sources of MSCs. These MSCs exhibit strong immunomodulatory properties that affect lymphocyte responses. The CD200/CD200R axis has been reported to be important in regulating the immune responses. Engagement of CD200R by CD200 initiates an inhibitory pathway that displays immunosuppressive effects. Because the CD200/CD200R axis is involved in immunoregulation, we investigated the expression and role of this ligand/receptor pair in MSCs and T-lymphocytes during co-culture. CD200 is differently expressed and modulated on MSCs depending on the tissue of origin and the culture conditions. Among the different MSC sources, WJ-MSCs express CD200 in the greatest proportion. This high constitutive CD200 expression may represent a distinctive marker for WJ-MSCs. A pro-inflammatory environment and IFN-γ in particular induce an increase in CD200 expression by BM-MSCs. In T-lymphocytes, CD200R and CD200 are differently distributed between the CD4(+) and CD8(+) T-cell subsets. During co-culture, blocking CD200-CD200R interactions does not prevent MSC-mediated inhibition of lymphocyte proliferation. However, depending on their origin, MSCs are able to modulate the expression of both CD200 and CD200R on some T-cells. Further study is required to understand the function of CD200 expression by nonmyeloid cells such MSCs and the significance of CD200 and C200R expression by T-cells. The findings presented here support bidirectional communication between MSCs and T-lymphocytes. Understanding the role of this ligand-receptor pair during co-culture will improve and increase the clinical use of MSCs.