Recombinant MHC tetramers for isolation of virus-specific CD8+ cells from healthy donors: Potential approach for cell therapy of posttransplant cytomegalovirus infection
- Authors: Vdovin A.S.1, Filkin S.Y.1, Yefimova P.R.1,2, Sheetikov S.A.1,2, Kapranov N.M.1, Davydova Y.O.1, Egorov E.S.3, Khamaganova E.G.1, Drokov M.Y.1, Kuzmina L.A.1, Parovichnikova E.N.1, Efimov G.A.1, Savchenko V.G.1
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Affiliations:
- National Research Center for Hematology
- Faculty of Biology
- Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
- Issue: Vol 81, No 11 (2016)
- Pages: 1371-1383
- Section: Molecular and Cellular Mechanisms of Inflammation (Special Issue) Guest Editors S. A. Nedospasov and D. V. Kuprash
- URL: https://journals.rcsi.science/0006-2979/article/view/151109
- DOI: https://doi.org/10.1134/S0006297916110146
- ID: 151109
Cite item
Abstract
Patients undergoing allogeneic hematopoietic stem cell transplantation have a high risk of cytomegalovirus reactivation, which in the absence of T-cell immunity can result in the development of an acute inflammatory reaction and damage of internal organs. Transfusion of the virus-specific donor T-lymphocytes represents an alternative to a highly toxic and often ineffective antiviral therapy. Potentially promising cell therapy approach comprises transfusion of cytotoxic T-lymphocytes, specific to the viral antigens, immediately after their isolation from the donor’s blood circulation without any in vitro expansion. Specific T-cells could be separated from potentially alloreactive lymphocytes using recombinant major histocompatibility complex (MHC) multimers, carrying synthetic viral peptides. Rapid transfusion of virus-specific T-cells to patients has several crucial advantages in comparison with methods based on the in vitro expansion of the cells. About 30% of hematopoietic stem cell donors and 46% of transplant recipients at the National Research Center for Hematology were carriers of the HLA-A*02 allele. Moreover, 94% of Russian donors have an immune response against the cytomegalovirus (CMV). Using recombinant HLA-A*02 multimers carrying an immunodominant cytomegalovirus peptide (NLV), we have shown that the majority of healthy donors have pronounced T-cell immunity against this antigen, whereas shortly after the transplantation the patients do not have specific T-lymphocytes. The donor cells have the immune phenotype of memory cells and can be activated and proliferate after stimulation with the specific antigen. Donor lymphocytes can be substantially enriched to significant purity by magnetic separation with recombinant MHC multimers and are not activated upon cocultivation with the antigen-presenting cells from HLA-incompatible donors without addition of the specific antigen. This study demonstrated that strong immune response to CMV of healthy donors and prevalence of HLA-A*02 allele in the Russian population make it possible to isolate a significant number of virus-specific cells using HLA-A*02–NLV multimers. After the transfusion, these cells should protect patients from CMV without development of allogeneic immune response.
About the authors
A. S. Vdovin
National Research Center for Hematology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167
S. Y. Filkin
National Research Center for Hematology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167
P. R. Yefimova
National Research Center for Hematology; Faculty of Biology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167; Moscow, 119991
S. A. Sheetikov
National Research Center for Hematology; Faculty of Biology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167; Moscow, 119991
N. M. Kapranov
National Research Center for Hematology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167
Y. O. Davydova
National Research Center for Hematology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167
E. S. Egorov
Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry
Email: efimov.g@blood.ru
Russian Federation, Moscow, 117997
E. G. Khamaganova
National Research Center for Hematology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167
M. Y. Drokov
National Research Center for Hematology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167
L. A. Kuzmina
National Research Center for Hematology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167
E. N. Parovichnikova
National Research Center for Hematology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167
G. A. Efimov
National Research Center for Hematology
Author for correspondence.
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167
V. G. Savchenko
National Research Center for Hematology
Email: efimov.g@blood.ru
Russian Federation, Moscow, 125167