Cytomegalovirus shapes long-term immune reconstitution after allogeneic stem cell transplantation

Abstract

Immune reconstitution after allogeneic stem cell transplantation is a dynamic and complex process depending on the recipient and donor characteristics, on the modalities of transplantation, and on the occurrence of graft-versushost disease. Multivariate methods widely used for gene expression profiling can simultaneously analyze the patterns of a great number of biological variables on a heterogeneous set of patients. Here we use these methods on flow cytometry assessment of up to 25 lymphocyte populations to analyze the global pattern of long-term immune reconstitution after transplantation. Immune patterns were most distinct from healthy controls at six months, and had not yet fully recovered as long as two years after transplant. The two principal determinants of variability were linked to the balance of B and CD8 + T cells and of natural killer and B cells, respectively. Recipient's cytomegalovirus serostatus, cytomegalovirus replication, and chronic graft-versus-host disease were the main factors shaping the immune pattern one year after transplant. We identified a complex signature of underand over-representation of immune populations dictated by recipient's cytomegalovirus seropositivity. Finally, we identified dimensions of variance in immune patterns as significant predictors of long-term non-relapse mortality, independently of chronic graft-versus-host disease.

CMV-specific immune reconstitution following allogeneic stem cell transplantation

“…66 CMV serostatus has a strong impact on the pattern of global immune recovery, such as the ratio of B cells to T and NK cells, in addition to the well known effects on T lymphocytes. 76 NK cell subsets recover early post transplant and are involved in the response to CMV, as are Vd2-negative gdT cells. 77,78 It is likely that NK cells contribute to control of CMV infection with expansions of IFN-g producing NK cell populations reported in response to and after resolution of CMV reactivation post HSCT.…”

Reconstitution of adaptive immunity after umbilical cord blood transplantation: impact on infectious complications

“…For example, CD8 + T cells recognizing periodically reactivated herpes viruses [i.e., cytomegalovirus (CMV) or Epstein Barr virus (EBV)] may expand rapidly. Therefore, as compared to that of the donor, the T-cell repertoire may narrow after alloHSCT and may be directed toward these viruses, specifically with grafts from adult donors that contain viral antigen-experienced memory T cells and in seropositive recipients (24)(25)(26).…”

CMV after transplant: T-cell repertoire crooks

“…4,5 In the posttransplant setting, CMV reactivation strongly associates with abnormal immune reconstitution. 6,7 In the present study, Suessmuth et al study how CMV reactivation affects T-cell dynamics in 17 patients who had myeloablative unrelated donor allogeneic transplant for myelodysplastic syndrome, acute leukemia, or myelofibrosis. These patients had posttransplant immune suppression with a calcineurin inhibitor and methotrexate with (n 5 10) and without abatacept (n 5 7).…”

“…With further follow-up, the benefit has remained for these groups of patients and is now evident in unfavorable risk, including FLT3-ITD-positive disease. 7 Other anthracyclines and dosing schedules of anthracyclines have recently been compared with daunorubicin. Most have demonstrated…”