[HTML][HTML] Memory CD4+ T cells do not induce graft-versus-host disease

BE Anderson, J McNiff, J Yan, H Doyle… - The Journal of …, 2003 - Am Soc Clin Investig
BE Anderson, J McNiff, J Yan, H Doyle, M Mamula, MJ Shlomchik, WD Shlomchik
The Journal of clinical investigation, 2003Am Soc Clin Investig
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 …
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 CD62LCD44+ 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 CD62LCD44+ 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.
The Journal of Clinical Investigation