Human CD62L- memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion.
Selective depletion of alloreactive T cells from allogeneic stem cell grafts can reduce graft-versus-host disease (GVHD) while preserving beneficial effects of T cells including facilitation of engraftment, protection against opportunistic infection, and reduced relapse risk. Memory T cells (CD62L(-)) represent a population of T cells that have previously encountered pathogens and may contain fewer T cells capable of recognizing neoantigens including recipient allogeneic antigen (aAg). We investigated whether human naive (CD62L(+)) or memory (CD62L(-)) T cells had different capacities to respond to aAg by assessing their ability to proliferate in response to and lyse HLA-mismatched Epstein-Barr virus-transformed B cells. Freshly sorted and in vitro expanded CD62L(-) memory T cells were less responsive to aAg stimulation than were CD62L(+) naive T cells but contained higher levels of cytomegalovirus (CMV)-specific T cells. Analysis of T cell receptor (TCR) repertoire showed restricted TCR diversity in the memory T-cell population possibly due to selection associated with chronic exposure to common pathogens. Memory T cells may represent a donor cell subpopulation suitable for enhancing immune reconstitution without increasing the risk of GVHD.
Foster
Aaron E
AE
Department of Medicine, Westmead Hospital, NSW, 2145, Australia.
Marangolo
Marina
M
Sartor
Mary M
MM
Alexander
Stephen I
SI
Hu
Min
M
Bradstock
Kenneth F
KF
Gottlieb
David J
DJ
D001402:B-Lymphocytes / Q000276:immunology; D002455:Cell Division; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D007519:Isoantigens / Q000276:immunology*; D019041:L-Selectin / Q000276:immunology*; D008212:Lymphocyte Depletion; D010641:Phenotype; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000235:genetics / Q000276:immunology; D013379:Substrate Specificity; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*
D007519:Isoantigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019041:L-Selectin