Yeh AC, Varelias A, Reddy A, et al. CMV Exposure Drives Long-Term CD57+ CD4 Memory T Cell Inflation Following Allogeneic Stem Cell Transplant. Blood. 2021; (doi: 10.1182/blood.2020009492).
For optimal immunologic outcomes after allogeneic stem cell transplant (allo-SCT), patients who are seronegative for cytomegalovirus (CMV) should preferentially receive grafts from donors who are also CMV seronegative. The reason is that previous exposure to CMV — even if CMV is not reactivated after allo-SCT — nurtures a highly expanded population of CD57+/CD27-CD4+ T cells. The cells, linked to reduced T cell receptor diversity and low numbers of blood major histocompatibility class (MHC) II-expressing antigen-presenting cells, are present at high volumes in CMV-specific T cells. Using 120 patient samples to validate their findings, the investigators determined that a CD4+/CD57+/CD27- T cell subset occupied an average of 19.6% of the total CD4+ T cell compartment when both donor and recipient were seropositive and 18% in cases with a seropositive recipient and seronegative donor. The percentage fell to 12% in seronegative recipient-seropositive donor matchups, and reached just 2.9% when paired donors and recipients were both seronegative. Researchers observed persistence in the T cell subset, which lingered for several years post-transplant. The study results support the argument that prior donor or recipient exposure to CMV irreversibly alters immunologic function after allo-SCT and, therefore, seronegative transplant recipients should receive seronegative grafts when at all possible.