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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2403-2409.
Prepublished online as a Blood First Edition Paper on July 1, 2004; DOI 10.1182/blood-2003-12-4431.
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IMMUNOBIOLOGY
Human CD62L– memory T cells are less responsive to alloantigen stimulation than CD62L+ naive T cells: potential for adoptive immunotherapy and allodepletion
Aaron E. Foster,
Marina Marangolo,
Mary M. Sartor,
Stephen I. Alexander,
Min Hu,
Kenneth F. Bradstock, and
David J. Gottlieb
From the Westmead Institute for Cancer Research, Westmead Millennium Institute, Westmead Hospital, Blood and Marrow Transplant Service, Westmead Hospital, Centre for Kidney Research, Children's Hospital at Westmead, and Department of Medicine, University of Sydney, Sydney, Australia.
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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