Epstein-Barr virus (EBV) and cytomegalovirus (CMV) can cause severe complications in patients undergoing allogeneic bone marrow transplantation. Virus-specific T lymphocytes play a critical role in controlling infection by these viruses.
We have used HLA tetramers to investigate the redevelopment of EBV specific immunity in patients following allogeneic bone marrow transplantation. In collaboration with the laboratories of Richard O'Reilly and Michel Sadelain, we are currently characterizing T cell receptor repertoires and avidities of EBV- and CMV-specific CD8 T cell populations in patients following allo-BMT and are testing the hypothesis that virus-specific T cell populations developing in transplant recipients have a narrower TCR repertoire when compared with the donor repertoire.
Our studies will determine whether a restricted TCR repertoire results in greater susceptibility to viral infection. HLA tetramers are also being used to estimate the relative avidities of EBV-specific T cells for cognate viral antigens. In additional studies we are investigating effector functions of EBV- and CMV-specific CD8 T cells in patients following allo-BMT. These studies are determining whether EBV- or CMV-specific T cells have deficiencies in effector functions following allo-BMT. We are measuring direct antigen-specific cytolytic activity and interferon-g, TNF, and MIP-1b expression by virus-specific CD8 T cells.
While CD8 T cells are important for defense against viral infection, it is clear that CD4 T cells also play an important role. We are characterizing CD4 T cell responses to EBV in bone marrow transplant recipients in order to correlate these T cell populations with the return and maintenance of virus-specific CD8 T cell function.
These studies are providing us with a deeper understanding of virus-specific immunity in the transplant patient and may lead to improved approaches for immune reconstitution. Additionally, these studies are beginning to characterize antiviral immune redevelopment in patients receiving related or unrelated and fully matched or partially mismatched allografts.
