Aberrant expression of HLA-DR antigen by bone marrow-derived mesenchymal stromal cells from patients affected by acute lymphoproliferative disorders.

摘要

Mesenchymal stromal cells (MSCs) can be isolated from various sources and their plasticity and multilineage potential to differentiate into other mesodermal cells has been widely reported. Host immune response has been the subject of numerous recent studies, in which it was demonstrated that MSCs have an immunomodulant role. Human MSCs have been shown to escape recognition by alloreactive T cells in mixed lymphocyte reaction cultures (MLR). The evidence that in vitro culture-expanded MSCs can be infused intravenously without toxicity have suggested that allogeneic MSC have many advantages in therapeutic applications such as enhancement of hematopoietic stem cells engraftment and reduction of the incidence and severity of graft-versus-host disease. The immunosuppressive nature of differentiated and undifferentiated bone-marrow (BM)-MSCs could also be of clinical importance in the treatment of autoimmune diseases.4 However, the mechanisms by which MSCs can exert their immunomodulant role are under investigation. Moreover, a few data are available in the literature regarding the heterogeneous pattern of response in inhibiting T-cell proliferation by cultured BM-MSCs from patients with hematological malignancies. In this study, the expression of human leukocyte antigen (HLA), major histocompatibility complex (MHC) class I and II were investigated on in vitro cultured BM-derived MSCs, based on the notion that either undifferentiated or differentiated MSCs express intermediate levels of HLA class I, but do not express the class II molecules. However, it is known that HLA-DR expression by MSCs can be induced by stimulation with interferon . Interestingly, both undifferentiated and differentiated MSCs do not express costimulatory molecules such as B7-1, B7-2, CD40 or CD40L and fail to elicit proliferation of allogeneic lymphocytes.