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Editorials
immune reconstitution after HLA-identical sibling HSCT in the absence of TD. The authors find that 60% and 11.5% of the TRα clonotypes in the patients’ memory and naïve T cells at day 180 post transplantation could be traced back to the donors’ memory repertoires, compared to only 30% and 15% to the donors’ naïve repertoires, respectively (Figure 2). These data suggest that the donor’s memory compartment is significantly reflected not only in the memory but also to a certain extent in the naïve CD8+ compartment after HLA-identical sibling HSCT. Given the high (>99%) purity of the FACS-sorted naïve and memory T-cell subsets used for the experi- ments, these intriguing findings are unlikely to have been impacted by sample spill-over. It should be noted that 2 of the 5 donors used for these analyses were cytomegalovirus (CMV) seropositive, while the remain-
ing 3 donors were seronegative. In transplants performed under PTCy regimen, donor CMV seropositivity has been shown to correlate significantly with a predominance of donor CD8+ memory T-cell reconstitution post transplan- tation.13 The data from Link-Rachner et al. suggest that this may hold true also for CMV seronegative donors in the non-TD setting, although a separate analysis of a larg- er number of seropositive and seronegative donors will be needed to verify this point.
The data also have potential practical implications. If the donor’s memory repertoire plays a leading role in shaping the patient’s repertoires after transplantation, the ‘quality’ of that donor memory repertoire might be assessed before transplant as a factor to be considered in donor selection, or as a prognostic tool for post-transplant complications. This observation becomes relevant also in
Figure 1. Impact of T-cell depletion (TD) on the size and diversity of the reconstituting naïve and memory CD8+ T-cell repertoires at six months post hematopoietic stem cell trans- plantation (HSCT). A schemat- ic representation of the donors’ (left) and the patients’ naïve (N) or memory (M) CD8+ T-cell repertoires at day 180 post transplantation (right), in the presence (TD) or absence (No TD) of TD by either anti-thy- mocyte globulin or post-trans- plant cyclophosphamide. The size of the bubbles indicates the approximate relative size of the repertoires. Within each bubble, CD8+ T cells of identi- cal T-cell receptor-α clonotypes are indicated by identical col- ors. A significant shrinking of both size and diversity of the naïve CD8+ T-cell repertoire occurs in the patient with TD compared to the patient with- out TD.
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