A mAb to SIRPα downregulates the priming of naive CD4+T cell in Primary immune thrombocytopenia

SIRP alpha is a transmembrane protein that binds the protein tyrosine phosphatases SHP-1 and SHP-2 through its cytoplasmic region and is abundantly expressed on monocytes, dendritic cells, and macrophages. Studies recently showed that SIRP alpha is essential for priming of CD4 + T cells by DCs and for development of Th17 cell-mediated autoimmune diseases. We have now further evaluated the importance of SIRP alpha and that of its ligand CD47 in primary immune thrombocytopenia (ITP). In this study, we show that there was a low expression state of SIRP alpha on the surface of monocytes. Treatment of cells culture from ITP patients with a mAb to SIRP alpha that blocks the binding of SIRP alpha to CD47 downregulated the ITP response. The abilities of monocytes from ITP patients to stimulate an allogenic MLR were reduced. The proliferation of, and production of IL-2, by CD4 + T cells from ITP patients were inhibited, the Treg cell numbers and the production of IL-10 pairs were upregulated, and the production of TGF-beta not was inhibited, by a mAb to SIRP alpha. Moreover, a mAb to SIRP alpha, the expression of HLA-DR and CD86 were markedly inhibited and the expression of CD80 was slightly upregulated, on the surface of CD14 + monocytes from ITP patients as compared with healthy subjects. However, blockade of SIRP alpha increased the secretion of TLR-dependent cytokines TNF-alpha, IL-6 and IL-1 beta by PBMCs, which may be considered as a reserve in response to danger signals. These results suggest that SIRP alpha on monocytes is essential for the priming of naive T cells and the development of ITP. Therefore, SIRP alpha is a potential therapeutic target for ITP and other autoimmune diseases.