PI-03. Influence of CMV serostatus of donor-recipient pairs on antiviral immunity reconstitution in the patients after allogeneic hematopoietic stem cell transplantation
Anna A. Dmitrova, Mikhail Yu. Drokov, Murad S. Vagida, Dmitriy O. Kiryukhin, Vera A. Vasilieva, Natalia N. Popova, Ekaterina D. Mikhaltsova, Mariya V. Dovydenko, Olga M. Koroleva, Daria S. Dubnyak, Zoya V. Konova, Mobil I. Akhmedov, Natalia M. Nikiforova, Uliyana V. Maslikova, Olga S. Starikova, Feruza A. Omarova, Elmira I. Kolgaeva, Dmitriy S. Tihomirov, Tatiana A. Tupoleva, Mikhail V. Demin, Larisa A. Kuzmina, Grigoriy A. Efimov, Elena N. Parovichnikova,
National Medical Research Center of Hematology, Moscow, Russia
Mikhail Yu. Drokov, e-mail: email@example.com
T cell-mediated immunity is the most important factor in the control of the cytomegalovirus infection (CMV infection). The most significant risk for developing CMV infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT) depends upon donor (D) and recipient (R) CMV serostatus. The interaction of these factors is still poorly understood. In our study we aimed to assess the effect of CMV serostatus of D/R pairs on the reconstitution of the antiviral immunity after allo-HSCT.
Patients and methods
Detailed characteristics of patients are presented in Table 1. The serological status of D/R pairs was determined at the stage before allo-HSCT. The samples of patients’ peripheral blood were examined at +30, +90, +180 days after allo-HSCT. CMV-specific T-lymphocytes were determined by flow cytometry using fluorochrome-labeled monoclonal antibodies against CD3, CD8, CD45 molecules, viability reagent and tetramers. The tetramers were consisted of in house produced MHC class I monomers loaded with one of three immunodominant epitopes of viral pp65 protein NLVPMVATV (NLV), TPRVTGGGAM (TPR), RPHERNGFTVL (RPH) peptides presented in HLA-A*02 and -B*07 conjugated with phycoerythrin loaded streptavidin. Further, to calculate the absolute number of T cells, a two-platform method was used. The total number of leukocytes was estimated using a Sysmex X-2100 hematology analyzer, which was later used to calculate the absolute number of CMV-specific cells.
Figure 1 shows that CMV-seronegative patients before allo-HSCT have lower number of CMV-specific T-cells up to +180 day after allo-HSCT compared to CMV-seropositive patients.
Thus, the reconstitution of CMV-specific immunity is influenced by primarily CMV infection before transplantation, which is most likely associated with the active proliferation of CMV-specific T-cells in response to antigenic stimulation.
Allogeneic hematopoietic stem cell transplantation, cytomegalovirus infection, cytomegalovirus reactivation, CMV-specific T-lymphocytes, immunosuppressive therapy, graft-versus-host disease.
Table 1. Patient characteristics
1 Fisher’s exact test; Kruskal-Wallis rank sum test
Figure 1. The number of CMV-specific T-cells (cells/μl) in the blood in patients at +30, +90, +180 days after allo-HSCT, depending on the CMV serostatus of the Donor-Recipient pairs (D/R)
* D–/R– – CMV seronegative donor/CMV seronegative recipient; * D–/R+ – CMV seronegative donor/CMV seropositive recipient; * D+/R– – CMV seropositive donor/CMV seronegative recipient; * D+/R+ – CMV seropositive donor/CMV seropositive recipient.