Myeloid-derived suppressor cells coexpressing both CD11b and Gr-1 antigens are a heterogeneous population of immature myeloid cells. Activation of inflammatory signaling through MyD88, presumably through ligation of multiple TLRs, plays a key role in the expansion of MDSCs. We investigated how the MyD88-dependent expansion of MDSCs from donor BM contributes to protection of GVHD. Lethally irradiated B6D2F1 mice were transplanted with C57BL/6 WT or MyD88 KO mice TCD-BM together with WT spleen T cells. Morbidity and mortality of GVHD were significantly worse in recipients of KO TCD-BM. The expression of MDSCs in blood, MLN and liver was reduced in the recipients of KO TCD-BM, whereas the percentage of donor T cells infiltrating gut and liver was markedly higher. In parallel, the percentages of donor T cells to undergo apoptosis in response to alloantigens in vivo were significantly decreased in recipients of KO TCD-BM. Moreover, in vivo administration of isolated MDSCs to recipients of KO TCD-BM attenuated the severity of GVHD. Administration of LPS to donor mice expanded MDSCs in BM with enhanced expression of MyD88 mRNAs. Recipients of TCD-BM from WT mice injected LPS also showed attenuated GVHD severity. In summary, MyD88-dependent expansion of MDSCs population from donor non T-cell component appears to be critical for attenuating GVHD severity. Incomplete expansion of MDSCs in target organs correlates with decreased apoptosis and increased infiltration of donor T cells.
- Copyright © 2013 by The American Association of Immunologists, Inc.