Naive and memory T cells induce different types of graft-versus-host disease.
The goal of this study was to compare the ability of donor naive and alloantigen-primed effector memory T cells to induce graft-vs-host disease after bone marrow transplantation in MHC-mismatched irradiated host mice. Purified CD4(+) naive (CD62L(high)CD44(low)) T cells and CD4(+) effector memory (CD62L(low)CD44(high)) T cells obtained from unprimed donors and donors primed to host alloantigens, respectively, were injected into host mice, and the rapidity, severity, and pattern of tissue injury of graft-vs-host disease was assessed. Unexpectedly, the naive T cells induced a more acute and severe colitis than the primed memory cells. Whereas the naive T cells expressing CD62L and CCR7 lymph node homing receptors vigorously expanded in mesenteric lymph nodes and colon by day 6 after transplantation, the primed memory T cells without these receptors had 20- to 100-fold lower accumulation at this early time point. These differences were reflected in the significantly more rapid decline in survival and weight loss induced by naive T cells. The primed memory T cells had a greater capacity to induce chronic colitis and liver injury and secrete IL-2 and IFN-gamma in response to alloantigenic stimulation compared with memory T cells from unprimed donors. Nevertheless, the expected increase in potency as compared with naive T cells was not observed due to differences in the pattern and kinetics of tissue injury.
Dutt
Suparna
S
Department of Medicine, Stanford University School of Medicine, CA 94305, USA.
Tseng
Diane
D
Ermann
Joerg
J
George
Tracy I
TI
Liu
Yin Ping
YP
Davis
Corrine R
CR
Fathman
C Garrison
CG
Strober
Samuel
S
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002908:Chronic Disease; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D006086:Graft vs Host Disease / Q000276:immunology* / Q000473:pathology; D018960:Hyaluronan Receptors / Q000276:immunology; D007156:Immunologic Memory; D007519:Isoantigens / Q000276:immunology*; D007700:Kinetics; D019041:L-Selectin / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000293:injuries / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009928:Organ Specificity / Q000276:immunology; D054400:Receptors, CCR7 / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous
C515371:Ccr7 protein, mouse; C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D007519:Isoantigens; D054400:Receptors, CCR7; D019041:L-Selectin