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Blood, 15 May 2008, Vol. 111, No. 10, pp. 5242-5251. Prepublished online as a Blood First Edition Paper on February 19, 2008; DOI 10.1182/blood-2007-09-107953.
TRANSPLANTATION Effects of donor T-cell trafficking and priming site on graft-versus-host disease induction by naive and memory phenotype CD4 T cells1 Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT; 2 Cancer Center and Department of Pediatrics, Division of Bone Marrow Transplantation, University of Minnesota, Minneapolis; Departments of 3 Pathology & Dermatology and 4 Pathology, Yale University School of Medicine, New Haven, CT; 5 Department of Pathology, University of Pittsburgh School of Medicine, PA; 6 Department of Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Cardiff, United Kingdom; 7 Section of Medical Oncology and Department of Immunobiology, Yale University School of Medicine, New Haven, CT; and 8 Departments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, CT
Graft-versus-host disease (GVHD) remains a major cause of morbidity and mortality in allogeneic stem cell transplantation. Effector memory T cells (TEM) do not cause GVHD but engraft and mount immune responses, including graft-versus-tumor effects. One potential explanation for the inability of TEM to cause GVHD is that TEM lack CD62L and CCR7, which are instrumental in directing naive T cells (TN) to lymph nodes (LN) and Peyer patches (PP), putative sites of GVHD initiation. Thus TEM should be relatively excluded from LN and PP, possibly explaining their inability to cause GVHD. We tested this hypothesis using T cells deficient in CD62L or CCR7, transplant recipients lacking PNAd ligands for CD62L, and recipients without LN and PP or LN, PP, and spleen. Surprisingly, CD62L and CCR7 were not required for TN-mediated GVHD. Moreover, in multiple strain pairings, GVHD developed in recipients that lacked LN and PP. Mild GVHD could even be induced in mice lacking all major secondary lymphoid tissues (SLT). Conversely, enforced constitutive expression of CD62L on TEM did not endow them with the ability to cause GVHD. Taken together, these data argue against the hypothesis that TEM fail to induce GVHD because of inefficient trafficking to LN and PP.
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