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.

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