The central nervous system is a target of acute graft versus host disease in mice

Hartrampf, Steffen, Dudakov, Jarrod A., Johnson, Linda K., Smith, Odette M., Tsai, Jennifer, Singer, Natalie V., West, Mallory L., Hanash, Alan M., Albert, Michael H., Liu, Bingfang, Toth, Miklos, and van den Brink, Marcel R.M. (2013) The central nervous system is a target of acute graft versus host disease in mice. Blood, 121 (10). pp. 1906-1910.

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Abstract

Despite significant advances in prevention and management, graft versus host disease (GVHD) is still a leading complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although skin, gut, liver, thymus, and lung are GVHD targets, neurological complications (NC) have also been reported following allo-HSCT. We demonstrate that the central nervous system (CNS) can be a direct target of alloreactive T cells following allo-HSCT in mice. We found significant infiltration of the CNS with donor T lymphocytes and cell death of neurons and neuroglia in allo-HSCT recipients with GVHD. We also found that allo-HSCT recipients with GVHD had deficits in spatial learning/memory and demonstrated increased anxious behavior. These findings highlight CNS sensitivity to damage caused by alloreactive donor T cells and represent the first characterization of target cell subsets and NC during GVHD. Therefore, these clinically relevant studies offer a novel and rational explanation for the well-described neurological symptoms observed after allo-HSCT.

Item ID: 29483
Item Type: Article (Research - C1)
ISSN: 1528-0020
Funders: National Institutes of Health, National Institute of Mental Health, US Department of Defense (USAMRAA Award), Radiation Effects Research Foundation (RERF-NIAID), Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center, Lymphoma Foundation, Alex’s Lemonade Stand Foundation (ALSF), Geoffrey Beene Cancer Research Center at Memorial Sloan-Kettering Cancer Center, Peter Solomon Fund, German Mehr-LEBEN-fur-krebskranke-Kinder - Bettina-Braeu-Stiftung, German Bayerische Forschungsstiftung Fellowship, Australian National Health and Medical Research Council, Leukemia and Lymphoma Society, Mr. William H. Goodwin and Mrs. Alice Goodwin
Date Deposited: 02 Oct 2013 23:48
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110708 Transplantation Immunology @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 40%
11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110903 Central Nervous System @ 20%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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