Regulation of Humoral Immunity
Mouse studies– The Bumgardner lab discovered that a novel subset of CD8+ T cells significantly inhibit the production of alloantibody in several transplant models (hepatocyte, islet, skin, and kidney). We have coined the term antibody-suppressor CD8+ T cells, or CD8+ TAb-supp cells. Current studies are aimed to investigate the mechanisms by which these CD8+ TAb-supp cells downregulate humoral immunity and to investigate their application as an autologous cellular immunotherapy to treat or prevent antibody-mediated rejection in transplant recipients.
Clinical studies– We have found that human kidney transplant recipients have a CD8+ T cell subset in their peripheral blood with the same phenotype as CD8+ TAb-supp cells. Interestingly, recipients who develop donor specific antibody (DSA) appear to have a deficit of this cell subset since they have far fewer of these cells compared to DSA-negative kidney transplant recipients. Current and future studies are aimed to determine if this human subset of CD8+ T cells are a homolog to the murine CD8+ TAb-supp cells.
Mouse Studies– We have found that innate natural killer T (iNKT) cells play a significant role in the generation of alloreactive responses following transplant (including humoral- and cellular-mediated rejection). Future and current studies are aimed to determine the precise mechanism of action that iNKT cells utilize to augment alloreactive response.