Effect of donor CD45RA-lymphocyte infusion on the T-cell subpopulation composition in adult patients after transplantation of allogeneic hematopoietic stem cells from a haploidentical donor with TCR αβ-depletion
Ulyana V. Maslikova, Natalia N. Popova, Mikhail Yu. Drokov, Julia O. Davydova, Nikolai M. Kapranov, Ekaterina D. Mikhaltsova, Vera A. Vasilieva, Maria V. Dovydenko, Olga M. Koroleva, Anna A. Dmitrova, Zoya V. Konova, Olga S. Starikova, Daria S. Dubnyak, Denis V. Kamelskikh, Irina V. Galtseva, Tatyana V. Gaponova, Miсhael A. Maschan, Larisa A. Kuzmina, Elena N. Parovichnikova, Valery G. Savchenko
National Medical Research Center of Hematology, Moscow, Russia
Contact: Dr. Ulyana V. Maslikova
Prevention of acute graft-versus-host (GVHD) reaction by means of TCRαβ-depletion technique in patients after allogeneic hematopoietic stem cell transplantation from a haploidentical donor (haplo-HSCT) is based on removal of αβT cells from the graft, thus leading to deep long-term immunodeficiency. Attempts to stimulate recovery of the immune system by transfusion of donor lymphocytes to the patients after haplo-HSCT are associated with extremely high risk of fatal GVHD. In pediatric practice, infusion of CD45RA- lymphocyte fraction allows to resolve this problem. However, effectiveness of this technique and its immunological aspects after haplo-HSCT in adult patients with TCR αβ-depletion are not yet been determined. Our aim was to evaluate the subpopulation composition of peripheral blood T-cells in adult patients after haplo-HSCT with TCR αβ-depletion with and without infusion of donor CD45RA lymphocytes.
Patients and methods
The study included 15 adult patients after haplo-HSCT with TCR αβ-depletion. In three cases, the donor CD45RA- lymphocytes were infused on day 0. To assess the subpopulation composition of T cells, we used flow cytometry technique (BD FACS Canto II, Becton Dickinson, USA). At day +30, the subpopulations of CD4 +, CD8 + T cells were determined in patients’ peripheral blood samples: T-naive and stem cell memory (Tnv + Tscm), i.e., CD45R0-CCR7 + CD28 +; central memory T cells (Tcm) including CD45R0+ CCR7+ CD28+; transitional memory T cells (Ttm) with CD45R0+ CCR7- CD28 + phenotype; T effector memory cells (Tem, CD45R0 + CCR7-CD28-); and terminal effector T cells (Tte) with CD45R0-CCR7-CD28- profile.
Results and conclusion
The subpopulation composition of CD4+, CD8+ T cells in patients after haplo-HSCT with TCR αβ-depletion with and without infusion of donor CD45RA- lymphocytes is shown in Figure 1.
Figure 1. The subpopulation composition of patients’ peripheral blood CD4+, CD8+ T cells at +30 days after haplo-HSCT with TCR αβ-depletion (the absolute number of cells per microliter is indicated)
The results showed that, by 30 days after haplo-HSCT, there were no significant differences in the CD4+, CD8+ T cell subpopulations in the patients after haplo-HSCT with TCR αβ-depletion with or without CD45RA- lymphocyte infusion. However, this may be due to a small sample of patients, and therefore it is advisable to conduct further research in this direction.
Allogeneic stem cell transplantation, TCR αβ-depletion, immune reconstitution.