Development of gammadelta T-cell receptor repertoire after TCRab/CD19 depleted haploidentical stem cell transplantation in children (P2190)

Abstract

Abstract Recent advances in stem cell manipulation techniques have allowed to optimize cellular composition of HLA-mismatched haploidentical stem cell grafts. We analyzed immune and haematopoietic reconstitution in 4 children transplanted with TCRab/CD19-depleted haploidentical stem cell grafts with a special emphasis on gammadelta-T-cell reconstitution. Grafts consisted of 8.5x10e6 CD34/kg, 8.8x10e4 CD3TCRab+/kg, 8.8x10e6 CD3TCRgd+/kg, and 17.5x10e6 CD16+CD56+/kg BW. Haematopoietic reconstitution was rapid in all patients. T-cell counts reached >100/µl after a median of 34 days, 75% of these expressing the gd-TCR. The predominance of gd-T-cells decreased and by day +100 50% of T-cells were positive for the gd-TCR and 46% for the ab-TCR. Gd-TCR Immunoscope analysis revealed the molecular composition of the gd-population: the Vg9-chain was expressed by a median of 54%, Vg2 by 17.6% of gd-T-cells, the remaining Vg-chains by less than 10%, respectively. Vd4-expressing subclones made up 53% of the whole gd-TCR-repertoire, followed by 33.4% Vd2+ subclones. Distribution of gd-subclones was relatively stable over time, so that the contraction of the gd-T-cell population could not be attributed to the disappearance of specific Vg- or Vd families. These data provide new insight into the T-cell reconstitution kinetics after TCRab/CD19-depleted transplantation.