MSC have the ability to differentiate into various types of connective tissue. Because interest in using these cells in a variety of transplant settings is high, we tested the immunologie properties of human bone marrow-derived MSC. MSC were stained with antibodies against cell surface antigens associated with various immune functions and were found to strongly express HLA class I, CD44 and CD90 (Thy-1), weakly express HLA class II and Fas ligand and not express B7-1, B7-2, CD40 or CD40L costimulatory molecules nor the Fas apoptotic receptor. After treatment with γ-interferon, both HLA class I and class II molecules were upregulated but B7-1 and B7-2 were not. To assess the ability of MSC to trigger T-cell responses, a mixed cell culture was performed by incubating peripheral blood lymphocytes (PBL) from normal volunteers with irradiated MSC derived from different individuals. Proliferation was measured by tritiated thymidine incorporation at days 4 and 6. There was no detectable stimulation of PBL by MSC, even after pretreatment of MSC with γ-interferon to upregulate HLA expression. To determine whether induction of anergy due to the lack of costimulatory molecules on MSC was responsible for absence of PBL stimulation, PBL were cocultured for 6 days with MSC isolated from HLA-DR7+ or HLA-DR7- individuals. PBL were then collected, rested and then restimulated with irradiated B lymphoblastoid cells homozygous for HLA-DR7. Increased thymidine incorporation by the PBL was seen in all cases, irrespective of the HLA type of the MSC used in the preculture, indicating that PBL viability was maintained after coculture with MSC and that alloantigen specific anergy had not been induced. To test whether active suppression by MSC was responsible for the lack of proliferation. PBL were stimulated with antibodies to CD3 and CD28 in the presence or absence of MSC. MSC completely abolished PBL activation. Addition of MSC-conditioned medium to PBL resulted in 30% inhibition of stimulation by anti-CD3 and anti-CD28. Medium conditioned by MSC and allogeneic PBL inhibited such proliferation by 70%. Therefore, MSC suppress PBL activation by mechanisms that do not involve induction of alloantigen-specific anergy and are at least in part dependent on soluble mediators. We speculate that the failure of MSC to stimulate proliferation by HLA-mismatched PBL, as well as their apparent suppression of T-cell activation, may confer unique advantages on MSC as an allogeneic stem cell source.
|Original language||English (US)|
|Issue number||11 PART I|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology