Allogeneic mesenchymal stem or stromal cells (MSCs) are proposed as cell therapies for degenerative, inflammatory,
and autoimmune diseases. The feasibility of allogeneic MSC therapies rests heavily on the concept that
these cells avoid or actively suppress the immunological responses that cause rejection of most allogeneic cells
and tissues. In this article the validity of the immune privileged status of allogeneic MSCs is explored in the
context of recent literature. Current data that provide the mechanistic basis for immune modulation by MSCs are
reviewed with particular attention to how MSCs modify the triggering and effector functions of innate and
adaptive immunity. The ability of MSCs to induce regulatory dendritic and T-cell populations is discussed with
regard to cell therapy for autoimmune disease. Finally, we examine the evidence for and against the immune
privileged status of allogeneic MSCs in vivo. Allogeneic MSCs emerge as cells that are responsive to local signals
and exert wide-ranging, predominantly suppressive, effects on innate and adaptive immunity. Nonetheless,
these cells also retain a degree of immunogenicity in some circumstances that may limit MSC longevity and
attenuate their beneficial effects. Ultimately successful allogeneic cell therapies will rely on an improved understanding
of the parameters of MSC–immune system interactions in vivo