Rapid reconstitution of CD4 T cells and NK cells protects against CMV-reactivation after allogeneic stem cell transplantation

Julia Drylewicz, Ingrid M. M. Schellens, Rogier Gaiser, Nening M. Nanlohy, Esther D. Quakkelaar, Henny Otten, Suzanne van Dorp, Ronald Jacobi, Leonie Ran, Sanne Spijkers, Dan Koning, Rob Schuurman, Ellen Meijer, Floortje L. Pietersma, Jurgen Kuball, Debbie van Baarle

Epstein-Barr virus and Cytomegalovirus reactivations frequently occur after allogeneic stem cell transplantation (SCT). Here we investigated the role of immune cell reconstitution in the onset and subsequent severity of EBV- and CMV-reactivation. To this end, 116 patients were prospectively sampled for absolute T cell (CD4 and CD8), B-cell (CD19) and NK-cell (CD16 and CD56) numbers weekly post-SCT during the first 3 months and thereafter monthly until 6 months post-SCT. Viral load was monitored in parallel. In contrast to the general belief, we found that early T-cell reconstitution does not play a role in the onset of viral reactivation. CMV reactivation in the first 7 weeks after SCT however resulted in higher absolute CD8(+) T-cell numbers 6 months post-SCT in patients with high-level reactivation, many of which were CMV-specific. Interestingly, rapid reconstitution of CD4(+) T-cells, as well as NK cells and the presence of donor KIR3DL1, are associated with the absence of CMV-reactivation after SCT, suggestive of a protective role of these cells. In contrast, EBV-reactivations were not affected in any way by the level of immune reconstitution after SCT. In conclusion, these data suggest that CD4(+) T-cells and NK cells, rather than CD8(+) T-cells, are associated with protection against CMV-reactivation.