Abstract 59: Platelets Have a Central Role in T Helper Cell Development and Responses

Abstract

Platelets are the primary cellular mediator of thrombosis, but platelets also have important roles in immune responses. Immune roles for platelets have been primarily explored in the context of endothelial cell interactions and innate immune responses, but our work now demonstrates an important and novel role for platelets in T cell development. Using the mouse abdominal cardiac transplantation model we have discovered that platelets have a central role in CD4+ T helper cell development and differentiation. Platelet deficient thrombopoietin receptor (TPOR/c-MPL) knockout mice given cardiac transplants have an accelerated rejection response driven by Th17 type of CD4+ T cell activation and infiltration of transplant tissue. These mice also have a basal skewing to Th17 development in the absence of transplantation. Platelets are the primary source of platelet factor 4 (PF4/CXCL4) and PF4-/- mice exhibit a very similar phenotype of unrestrained Th17 T cell development and responses post transplantation as the TPOR-/- mice. Furthermore, PF4 directly limits in vitro Th17 cell differentiation, demonstrating that platelets via PF4 have a major prior unrecognized role in T helper cell differentiation. Taken together, these data demonstrate a highly novel platelet function in T helper cell development. PF4 has a direct effect on maintaining T cell homeostasis and differentiation which is highly relevant to transplant immune responses and chronic rejection.