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 Blood, 1 April 2007, Vol. 109, No. 7, pp. 3115-3123.
Prepublished online as a Blood First Edition Paper on December 5, 2006; DOI 10.1182/blood-2006-04-016410.

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TRANSPLANTATION

Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponse

Benny J. Chen1, Divino Deoliveira1, Xiuyu Cui1, Ngocdiep T. Le1, Jessica Son1, John F. Whitesides2, and Nelson J. Chao1

1 Division of Cellular Therapy/Bone Marrow Transplantation, 2 Human Vaccine Institute, Department of Medicine and Immunology, Duke University Medical Center, Durham, NC

Several groups, including our own, have independently demonstrated that effector memory T cells from non–alloantigen-primed donors do not cause graft-versus-host disease (GVHD). In the current study, we further investigated whether this approach could be extended to all memory T cells, and we studied the underlying mechanisms. Neither total memory T cells nor purified central memory T cells were able to induce GVHD. Memory T cells were at least 3-log less potent than bulk T cells in mediating GVHD. As expected, memory T cells failed to elicit cytotoxicity and proliferated poorly against alloantigens in standard 5-day mixed-lymphocyte cultures. However, the proliferative responses of memory T cells were more comparable with those of bulk and naive T cells when the culture time was shortened. Moreover, the frequencies of IL-2–secreting cells measured by 42-hour enzyme-linked immunosorbent spot (ELISPOT) assay were similar among naive, memory, and bulk T cells. These data indicated that memory T cells are able to respond to alloantigens initially but fail to develop to full potential. The abortive immune response, which was mediated by non–alloantigen-specific memory T cells in response to alloantigens, may explain why memory T cells from unprimed and non–alloantigen-primed donors could not induce GVHD.


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Naive and Memory T Cells Induce Different Types of Graft-versus-Host Disease
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