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Blood, 15 June 2007, Vol. 109, No. 12, pp. 5502-5510. Prepublished online as a Blood First Edition Paper on March 8, 2007; DOI 10.1182/blood-2006-12-061713. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-12-061713v1 109/12/5502    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Gorski, J. Articles by Drobyski, W. R. Search for Related Content PubMed PubMed Citation Articles by Gorski, J. Articles by Drobyski, W. R. Related Collections Transplantation Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Homeostatic expansion and repertoire regeneration of donor T cells during graft versus host disease is constrained by the host environment Jack Gorski1, Xiao Chen2,3, Mariya Gendelman2,3, Maryam Yassai1, Ashley Krueger1, Elizabeth Tivol2,3, Brent Logan4, Richard Komorowski5, Sanja Vodanovic-Jankovic2,3, and William R. Drobyski2,3 1 Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI; 2 Bone Marrow Transplant Program, Medical College of Wisconsin, Milwaukee, WI; 3 Department of Medicine, Medical College of Wisconsin, Milwaukee, WI; 4 Department of Biostatistics and 5 Pathology, Medical College of Wisconsin, Milwaukee, WI Graft versus host disease (GVHD) typically results in impaired T-cell reconstitution characterized by lymphopenia and repertoire skewing. One of the major causes of inadequate T-cell reconstitution is that T-cell survival and expansion in the periphery are impaired. In this report, we have performed adoptive transfer studies to determine whether the quantitative reduction in T-cell numbers is due to an intrinsic T-cell defect or whether the environmental milieu deleteriously affects T-cell expansion. These studies demonstrate that T cells obtained from animals with graft-versus-host disease (GVHD) are capable of significant expansion and renormalization of an inverted CD4/CD8 ratio when they are removed from this environment. Moreover, these cells can generate complex T-cell repertoires early after transplantation and are functionally competent to respond to third-party alloantigens. Our data indicate that T cells from mice undergoing GVHD can respond to homeostatic signals in the periphery and are not intrinsically compromised once they are removed from the GVHD environment. We thereby conclude that the host environment and not an intrinsic T-cell defect is primarily responsible for the lack of effective T-cell expansion and diversification of complex T-cell repertoires that occurs during GVHD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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