CMV reactivation drives post-transplant T cell reconstitution and results in defects in the underlying TCRβ repertoire

Origin and evolution of the T cell repertoire after posttransplantation cyclophosphamide

“…Given our finding that CMV appears to play a more prominent role than aGVHD in T cell repertoire skewing in both PTCy- and CNI-treated patients, CMV also may be a confounder for aGVHD in that umbilical cord blood study. As the dominant effect of CMV in shaping immune reconstitution has now been reported by several groups (23, 24, 48), it is likely that at least some of our findings pertain more broadly to other transplantation platforms.…”

“…More recently, the substantial impact that CMV has on shaping lymphocyte reconstitution in patients undergoing alloBMT has been appreciated (23, 24, 48), although there has been no consensus achieved over whether CMV seropositivity or detectable CMV reactivation plays the dominant role. Consistent with a previous report (23), we found that recipient CMV seropositivity appears to have a more significant impact on CD8 + and CD4 + EM and TEMRA numerical recovery after transplant than does CMV reactivation, particularly in the early posttransplant period.…”

“…Although CMV may play a dominant role, posttransplant numerical reconstitution of T cells is also likely driven by other pathogens, including EBV (49, 50). Whether latent viral infections and the associated memory inflation that consequently occurs within the EM and TEMRA T cell subsets contribute to functional impairment in the T cell repertoires in our patients requires further evaluation (48, 51). …”

Reconstitution of T Cell Immunity after Umbilical Cord Blood Transplantation

“…The overarching conclusion of studies on immune reconstitution has been that lack of diversity or skewing of the T cell repertoire increases the risk of infections, NRM, death, and potentially GVHD [7,8]. Adoptive therapy with virus-specific T cells or other T cell populations expanded ex vivo can provide protection against specific pathogens but may not be sufficient to robustly augment T cell repertoire diversity.…”

Origin and evolution of the T-cell repertoire after posttransplantation cyclophosphamide

“…The profound influence of CMV on the immune system in clinically healthy individuals is well documented (44)(45)(46)(47). More recently, the substantial impact that CMV has on shaping lymphocyte reconstitution in patients undergoing alloBMT has been appreciated (23,24,48), although there has been no consensus achieved over whether CMV seropositivity or detectable CMV reactivation plays the dominant role. Consistent with a previous report (23), we found that recipient CMV seropositivity appears to have a more significant impact on CD8 + and CD4 + EM and TEMRA numerical recovery after transplant than does CMV reactivation, particularly in the early posttransplant period.…”