SOCS3 Regulates Th1 Dependent Acute Graft-Versus Host Disease

• Published in: Blood 2008-11, Vol.112 (11), p.3513-3513
• Main Authors: MacDonald, Kelli P A, Kuns, Rachel D, Don, Alistair LJ, Olver, Stuart D, Raffelt, Neil C, Markey, Kate A, Alexander, Warren, Roberts, Andrew W., Hill, Geoff R
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V112.11.3513.3513

G-CSF mobilized peripheral blood has emerged as the dominant source of stem cells for allogeneic stem cell transplantation. G-CSF modulates T cell function and Suppressor of Cytokine Signaling-3 (SOCS3) is the major regulator of signaling by this cytokine, although the downstream effects in vivo remain unclear. We have therefore examined the effect of SOCS3 in the well established B6 → B6D2F1 murine model of acute GVHD directed to major histocompatibility antigens. Using SOCS3−/Δvav mice in which SOCS3 deficiency is restricted to the haematopoietic compartment we transplanted splenocytes from G-CSF mobilized wild-type (WT) or SOCS3−/Δvav donors and demonstrated that the absence of SOCS3 within the graft accelerated GVHD (median survival 23 vs. 39 days, P=0.04). By using SOCS3−/ΔLysM and SOCS3−/Δlck donors in which SOCS3 deficiency was restricted to the myeloid or T cell lineage respectively we confirmed SOCS3 deficiency enhanced GVHD via effects only within the donor T cell (median survival 19 vs. 35 and 39 days in SOCS3−/Δlck vs. WT and SOCS3−/ΔLysM, P