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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2988-2990.
Prepublished online as a Blood First Edition Paper on December 2, 2004; DOI 10.1182/blood-2004-07-2646.


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TRANSPLANTATION
Brief report

Leydig cell injury as a consequence of an acute graft-versus-host reaction

Anna-Margaretha Wagner, Konstantin Beier, Elli Christen, Georg A. Holländer, and Werner Krenger

From the Departments of Research and Clinical-Biological Sciences, Center for Biomedicine, University of Basel, Basel, Switzerland; University Children's Hospital (UKBB), Basel, Switzerland; and the Institute of Anatomy, University of Basel, Basel, Switzerland.

Hematopoietic stem cell transplantation (HSCT) is associated with significant posttransplantation gonadotoxicity. This deficit has been mainly attributed to pretransplantation conditioning, but lower sperm counts in humans also appear to be associated with graft-versus-host disease (GVHD) following allogeneic HSCT. However, the mechanisms leading to diminished spermatocyte levels during GVHD remain unknown. Here we demonstrate that injury to intratesticular cells occurs in unconditioned F1 mice following the infiltration of donor alloreactive T cells during an acute graft-versus-host reaction (GVHR). Using computer-aided quantitative microscopic morphometry we demonstrate that the nadir of Leydig cell volume density coincides with the peak of intratesticular infiltration by donor T cells. Injury to Leydig cells correlates with an intratesticular inflammatory response characterized by interferon-{gamma} and tumor necrosis factor-{alpha} production. These results demonstrate impairment of testosterone-producing Leydig cells during a local alloresponse, thus representing a mechanism that contributes to gonadal insufficiency following allogeneic HSCT.


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