TY - JOUR
T1 - Human CD62L- memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells
T2 - Potential for adoptive immunotherapy and allodepletion
AU - Foster, Aaron E.
AU - Marangolo, Marina
AU - Sartor, Mary M.
AU - Alexander, Stephen I.
AU - Hu, Min
AU - Bradstock, Kenneth F.
AU - Gottlieb, David J.
PY - 2004/10/15
Y1 - 2004/10/15
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2003-12-4431
DO - 10.1182/blood-2003-12-4431
M3 - Article
C2 - 15231569
AN - SCOPUS:4944252715
SN - 0006-4971
VL - 104
SP - 2403
EP - 2409
JO - Blood
JF - Blood
IS - 8
ER -