Distinct patterns of regeneration of central memory, effector memory and effector TCD8+ cell subsets after different hematopoietic cell transplant types: possible influence in the recovery of anti-cytomegalovirus immune response and risk for its reactivation.
TCD8+ cells may be divided into subsets with different phenotypes and functions: naive, central memory, effector memory and effector. Aiming to better understand the differences in early reconstitution of these TCD8+ cell subsets and their relationship with post-transplant anti-cytomegalovirus (CMV) immune responses recovery, we prospectively analyzed the transfer and expansion of these subsets in different transplant types. We found that graft cells from donor's peripheral blood, either allogeneic or autologous, were enriched for central memory, effector memory and effector phenotypes compared to allogeneic bone marrow grafts, as assessed by surface markers phenotyping and granzyme B expression. However, post-transplant, these subsets expanded in autologous recipients only, reaching numbers much greater than in allo-recipients at days +29 and +96. At the same time, autologous recipients presented less CMV reactivation and more vigorous CMV-induced interferon-gamma and lymphoproliferative responses. The marked loss of allo-transferred memory TCD8+ cells was probably due to the fact that they were more activated and more prone to apoptosis than auto-transferred TCD8+ cells as assessed by CD69 and active caspase 3 expression. Thus, transfer of peripheral blood stem cells in the allogeneic but not autologous setting is associated with poor expansion of memory TCD8+ cells, probably delaying antiviral immune reconstitution. These data may have important implications for the design of better strategies to immunoprotect this population against infectious challenges since different transplant types have different potentials for memory TCD8+ cells transfer and expansion.
Ferrari
Valeria
V
Laboratory of Dermatology and Immunodeficiencies (LIM-56), Medical School of the University of São Paulo, Av. Dr. Enéas de Carvalho Aguiar 500 3rd Floor, São Paulo, Brazil.
Cacere
Camila Rodrigues
CR
Machado
Clarisse Martins
CM
Pannuti
Claudio Sérgio
CS
Dulley
Frederico Luiz
FL
Barros
José Carlos Antonio
JC
Duarte
Alberto José da Silva
AJ
Benard
Gil
G
D000328:Adult; D017209:Apoptosis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D053804:Granzymes; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D012697:Serine Endopeptidases / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases