Divide and conquer: Blocking graft versus host but not graft versus leukemia T cells with agonist BTLA co-inhibitory signals.

Abstract

One of the main objectives in allogeneic hematopoietic stem cell transplantation (aHSCT) research is the prevention of graft versus host disease (GVHD) while maintaining the graft versus leukemia/lymphoma (GVL) effect. Whether these two responses generated by donor T cells can be sufficiently separated and controlled remains controversial. While various approaches have been tested to achieve this goal, success has been relatively limited. Lymphocyte responses are negatively regulated by a series of receptors that function along with antigen receptors to deliver co-inhibitory signals. B and T lymphocyte associated (BTLA) is a novel co-inhibitory molecule expressed by activated T cells, B cells and other immune cells. A study by Albring et al. has now shown in a murine model that a single injection of agonistic anti-BTLA monoclonal antibody can inhibit GVHD long-term while maintaining GVL responses and immunity to infection. These studies suggest that future development of biologics to harness the function of co-inhibitory signals will be an important approach in the prevention of autoimmunity and GVHD and in protocols to achieve transplantation tolerance.