Inability of memory T cells to induce graft-versus-host disease is a result of an abortive alloresponse.
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.
Chen
Benny J
BJ
Division of Cellular Therapy/Bone Marrow Transplantation, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. chen0032@mc.duke.edu
Deoliveira
Divino
D
Cui
Xiuyu
X
Le
Ngocdiep T
NT
Son
Jessica
J
Whitesides
John F
JF
Chao
Nelson J
NJ
D000818:Animals; D020296:Animals, Congenic; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007519:Isoantigens / Q000008:administration & dosage; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D033581:Stem Cell Transplantation / Q000009:adverse effects; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D007519:Isoantigens; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin