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T-cell receptors following SCT
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Figure 1. CD4+ and CD8+ T-cell subsets. Immune reconstitution of T-cell subsets of CD4+ T cells (A) and CD8+ T cells (B) on day 60 (d60), day 120 (d120) and day 180 (d180) post transplantation. Patient groups with 5 patients were analyzed separately and compared to the control population (C, n=20).
CCR7+CD45RA+ naïve CD8+ T cells was also suppressed within all groups compared to those of controls (P<0.001). Again, the lowest counts were seen in patients receiving ATG and PTCy, but these counts were not statistically sig- nificant. CD8+ T cells were primarily composed of EM cells and TEMRA cells for all groups. Both the EM and TEMRA fractions were comparable to or higher than those in the reference group, with differentiated cells becoming the dominant population over time (EM, P<0.01 on day 60; TEMRA, P<0.01 on day 120 and P<0.001 on day 180); no significant differences were seen between the transplantation groups (Figure 1B).
T-cell receptor-α repertoire composition and diversity are shaped by the memory T-cell receptor-α repertoire of the donor
We had access to blood samples from 5 donors at the time of transplant donation (Online Supplementary Table S1) allowing us to directly compare their repertoires with those of the recipients. While the correlation of memory diversity between donor and recipient was not significant (likely due to the low number of samples), the correlation was stronger on day 180 (r2=0.6602) than on day 60 (r2=0.5484).
The recipients’ repertoires were heavily shaped by the memory repertoires of the donors. We found that 77.2% and 80.0% of the TRα reads from the donors' memory repertoires were populated by clonotypes shared by donors’ and patients’ memory repertoires on days 60 and 180, respectively. Notably, 41.5% (on day 60) and 61.0% (on day 180) of the donors’ memory repertoires were also found in the naïve repertoires of the recipients. In con- trast, only 8.9% and 10.1% of the donors’ naïve reper- toires were recovered in the recipients’ memory reper- toires, and 6.0% and 18.6% were recovered in the recipi- ents’ naïve repertoires on days 60 and 180, respectively (Figure 2A).
Clinical context of T-cell receptor-α repertoire composition in SIB-noATG patients
Among SIB-noATG patients, 3 out of 5 patients (TCR_011, TCR_024, TCR_040) revealed highly domi- nant memory clonotypes (defined as >10% of repertoire) that either were not dominant or were not even found in their donor’s repertoire (Figure 2C).
The medical history of 2 patients (TCR_024 and TCR_040) who developed highly dominant clonotypes accompanied by a decrease in TCR memory diversity
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