CMV exposure drives long-term CD57+ CD4 memory T-cell inflation following allogeneic stem cell transplant

Donor and recipient cytomegalovirus (CMV) serostatus correlate with transplant-related mortality that is associated with reduced survival following allogeneic stem cell transplant (SCT). Prior epidemiologic studies have suggested that CMV seronegative recipients (R-) receiving a CMV-seropositive graft (D+) experience inferior outcomes compared with other serostatus combinations, an observation that appears independent of viral reactivation. We therefore investigated the hypothesis that prior donor CMV exposure irreversibly modifies immunologic function after SCT. We identified a CD4(+)/CD57(+)/CD27(-) T-cell subset that was differentially expressed between D+ and D- transplants and validated results with 120 patient samples. This T-cell subset represents an average of 2.9% (D-/R-), 18% (D-/R+), 12% (D+/R-), and 19.6% (D+/R+) (P < .0001) of the total CD4(+) T-cell compartment and stably persists for at least several years post-SCT. Even in the absence of CMV reactivation postSCT, D+/R- transplants displayed a significant enrichment of these cells compared with D-/R- transplants (P = .0078). These are effector memory cells (CCR7-/CD45RA(+/-)) that express T-bet, Eomesodermin, granzyme B, secrete Th1 cytokines, and are enriched in CMV-specific T cells. These cells are associated with decreased T-cell receptor diversity (P < .0001) and reduced proportions of major histocompatibility class (MHC) II expressing classical monocytes (P < .0001), myeloid (P = .024), and plasmacytoid dendritic cells (P = .0014). These data describe a highly expanded CD4(+) T-cell population and putative mechanisms by which prior donor or recipient CMV exposure may create a lasting immunologic imprint following SCT, providing a rationale for using D- grafts for R- transplant recipients.

Automated summary

Studies show that the CMV serostatus of donors and recipients is associated with transplant-related mortality following allogeneic stem cell transplant (SCT). Previous research has indicated that CMV-seronegative recipients receiving a CMV-seropositive graft may have inferior outcomes compared to other serostatus combinations, even without viral reactivation. This suggests that prior CMV exposure can have lasting effects on immune function after SCT.