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      Naive and memory T cells induce different types of graft-versus-host disease.

      The Journal of Immunology Author Choice
      Animals, Antigens, CD44, immunology, Bone Marrow Transplantation, CD4-Positive T-Lymphocytes, pathology, Chronic Disease, Colitis, Graft vs Host Disease, Immunologic Memory, Isoantigens, Kinetics, L-Selectin, Liver, injuries, Liver Diseases, Male, Mice, Mice, Inbred BALB C, Organ Specificity, Receptors, CCR7, Time Factors, Transplantation, Homologous

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          Abstract

          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.

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