Immune Mechanisms Important for the Pathogenesis of Graft-Versus-Host Disease

 

Trainee:

LeShara Fulton

lesharafulton

Research Mentor

Dr. Jonathan Serody, MD

serody

Clinical Co-mentor

Dr. Kimberly Kasow, MD

kasow

Clinical Co-Mentor

Dr. Stephanie Sarantopoulos, MD

unavailable
Home Department Microbiology and Immunology
Project Description

Allogeneic hematopoietic stem-cell transplantation is the treatment of choice for patients with high risk acute leukemia, recurrent leukemia, bone marrow failure syndromes and is commonly utilized for the treatment of indolent lymphomas. One significant consequence of allogeneic stem cell (Allo SCT) transplantation is the occurrence of acute graft-versus-host disease (aGvHD), which is mediated by mature T cells present in the donor marrow or stem cell inoculums. GvHD occurs in 30-60% of individuals that undergo an allogeneic SCT and can cause significant morbidity and mortality in this patient population.

One aspect of the biology of GvHD that has received attention recently has been the role of migratory proteins found on donor T cells in the migration of donor cells to the initial sites of activation. This work has shown that donor T cells initially migrate to lymphoid tissue of the host where they are activated by host antigen presenting cells. This activation changes the expression of migratory proteins on the surface of donor T cells allowing them to migrate to GvHD target tissue. Recent work has suggested that inhibiting the migration of donor T cells into or out of the lymphoid tissue has a significant effect on the incidence and severity of acute GvHD. Coronin 1A (Coro 1A) an actin binding protein found in immune and hematopoietic tissue plays a critical role in T cell migration. Previous data has shown a protective effective of Coro 1A-/- T cells in aGvHD. Based on these data I will evaluate the function of Coro 1A in the pathogenesis of aGvHD.

Determining specific T cell populations responsible for the pathogenesis of GvHD is critical for improved therapies. Studies in our laboratory have demonstrated that TH17 cells are able to mediate GvHD, characterized by extensive skin and pulmonary inflammation. My research will continue the investigation of TH17 cells involvement in GvHD and possible targeting this cell population for novel clinical therapies.