NIV Congres

We have recently shown that lymph nodes (LN) contain hCMV-specific CD8⁺ T cells that resemble central memory cells, a phenotype that is not found in peripheral blood (PB). We have also shown that the LN hCMV-pp65-specific CD8⁺ T cell pool contained clones not found in PB. It is not known what the contribution of these LN hCMV-specific CD8⁺ T cells is to the PB pool upon viral recall. We therefore studied the contribution of these clones to the PB pool during CMV reactivation.

Two patients experiencing a hCMV reactivation after kidney transplantation were studied. hCMV-pp65-specific CD8⁺ T cells of pre transplantation LN and paired PB, as well as PB obtained during reactivation and 1 year after transplantation were analyzed for clonal relationships by high-throughput-sequencing of the TCR-Vβ-CDR3 region.

In the first patient the PB pool was restricted to one clone and the LN pool consisted of an identical clone and one extra unique clone. During two subsequent reactivations the CMV-specific pool remained restricted to the same dominant clone. Though the unique LN clone did not contribute to the PB pool, it could not be determined whether the vigorous expansion of the CMV-specific pool during both reactivations was caused by the LN derived clone or the PB derived clone, since both clones were identical. In the second patient both overlapping and unique clones were present in LNs and PB.  The unique LN derived clones could be found to add substantially to the PB pool upon reactivation. In fact, at that time point the major clone was a LN derived one. However, also in this patient, not all unique LN clones added to the PB pool upon reactivation.

In conclusion, LNs seem to harbor a unique pool of ‘true’ memory hCMV-pp65-specific CD8⁺ T cells that proliferate vigorously and contribute to the PB population upon antigenic recall.