Research Group

  • Dr Andrew Luster, Principal Investigator
  • Dr Edward Seung, Research Associate


  • Massachusetts General Hospital, Charlestown, USA


  • Chemokine-Mediated Control of Effector and Regulatory T Cells in Lung Rejection

Lung transplantation remains the only effective therapy for the large number of patients with end-stage lung disease. However, despite advances in immunosuppressive therapies and surgical techniques, overall 5-year survival remains less than 50%, the worst among the major solid organ transplants. The pathologic process involved in lung rejection is still poorly understood, but clinical studies have implicated lung injury from acute rejection (AR) as the major causative factor. Effector T cells specific for the donor lung are critical mediators of AR, but the factors that determine their generation and function are not fully known. Ischemia-reperfusion (IR) injury and viral infection are important risk factors for rejection and thus may be important inducers of effector T cell formation.

In an effort to study these factors, we have developed a transgenic mouse model of lung rejection, where adoptive transfer of antigen-specific effector T cell induces pulmonary AR and death. However, this phenotype does not occur when naïve antigen-specific T cells are transferred. In this proposal, we will address the following questions: 1) do the clinically relevant factors of I-R and infection induce the differentiation of naïve T cells into effector T cells, 2) where and how do T cells need to traffic to induce pulmonary AR, and 3) where and how do regulatory T cells (Tregs) need to traffic to prevent pulmonary AR.

In order to answer these questions, we will determine if influenza virus infection or IR can induce the generation of effector T cells and lung AR in our transgenic mice injected with naïve antigen-specific T cells. Next, we will use antigen-specific T cells from mice deficient in specific chemokine receptors to determine which receptor deficiency prevents effector T cell generation and function. Lastly, we will use mice deficient in chemokine receptors expressed by Tregs to determine where Tregs function and which receptors are important for their suppressive function. We will use cutting edge microscopy to track the migratory behavior of effector T cells and Treg in vivo in real time. This proposal will define the critical chemokine receptors involved in generation and delivery of effector T cells and Tregs into the transplanted lung and should provide new therapeutic targets to prevent and treat AR.

Progress Report
Final Report