Memory CD4+ T cells do not induce graft-versus-host disease.
Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation (alloSCT). Donor T cells that accompany stem cell grafts cause GVHD by attacking recipient tissues; therefore, all patients receive GVHD prophylaxis by depletion of T cells from the allograft or through immunosuppressant drugs. In addition to providing a graft-versus-leukemia effect, donor T cells are critical for reconstituting T cell-mediated immunity. Ideally, immunity to infectious agents would be transferred from donor to host without GVHD. Most donors have been exposed to common pathogens and have an increased precursor frequency of memory T cells against pathogenic antigens. We therefore asked whether memory CD62L-CD44+ CD4+ T cells would induce less GVHD than unfractionated or naive CD4+ T cells. Strikingly, we found that memory CD4 cells induced neither clinical nor histologic GVHD. This effect was not due to the increased number of CD4+CD25+ regulatory T cells found in the CD62L-CD44+ fraction because memory T cells depletion of these cells did not cause GVHD. Memory CD4 cells engrafted and responded to antigen both in vivo and in vitro. If these murine results are applicable to human alloSCT, selective administration of memory T cells could greatly improve post-transplant immune reconstitution.
Anderson
Britt E
BE
Sections of Immunobiology,Yale University School of Medicine, New Haven, Connecticut 06520, USA.
McNiff
Jennifer
J
Yan
Jun
J
Doyle
Hester
H
Mamula
Mark
M
Shlomchik
Mark J
MJ
Shlomchik
Warren D
WD
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D006086:Graft vs Host Disease / Q000209:etiology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D018960:Hyaluronan Receptors / Q000032:analysis; D007156:Immunologic Memory; D019041:L-Selectin / Q000032:analysis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000032:analysis
D018960:Hyaluronan Receptors; D015375:Receptors, Interleukin-2; D019041:L-Selectin