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Blood, 15 January 2007, Vol. 109, No. 2, pp. 819-826. Prepublished online as a Blood First Edition Paper on September 14, 2006; DOI 10.1182/blood-2006-03-008219. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-03-008219v1 109/2/819    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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Brehm, M. A. Articles by Greiner, D. L. Search for Related Content PubMed PubMed Citation Articles by Brehm, M. A. Articles by Greiner, D. L. Related Collections Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  TRANSPLANTATION Rapid quantification of naive alloreactive T cells by TNF- production and correlation with allograft rejection in mice Michael A. Brehm1,, Julie Mangada2, Thomas G. Markees2, Todd Pearson2, Keith A. Daniels1, Thomas B. Thornley2, Raymond M. Welsh1, Aldo A. Rossini2, and Dale L. Greiner2 1 Department of Pathology and 2 Department of Medicine, University of Massachusetts Medical School, Worcester, MA Allograft transplantation requires chronic immunosuppression, but there is no effective strategy to evaluate the long-term maintenance of immunosuppression other than assessment of graft function. The ability to monitor naive alloreactive T cells would provide an alternative guide for drug therapy at early, preclinical stages of graft rejection and for evaluating tolerance-inducing protocols. To detect and quantify naive alloreactive T cells directly ex vivo, we used the unique ability of naive T cells to rapidly produce TNF- but not IFN-. Naive alloreactive T cells were identified by the production of TNF- after a 5-hour in vitro stimulation with alloantigen and were distinguished from effector/memory alloreactive T cells by the inability to produce IFN-. Moreover, naive alloreactive T cells were not detected in mice tolerized against specific alloantigens. The frequency of TNF-–producing cells was predictive for rejection in an in vivo cytotoxicity assay and correlated with skin allograft rejection. Naive alloreactive T cells were also detected in humans, suggesting clinical relevance. We conclude that rapid production of TNF- can be used to quantify naive alloreactive T cells, that it is abrogated after the induction of tolerance, and that it is a potential tool to predict allograft rejection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. B. Thornley, N. E. Phillips, B. C. Beaudette-Zlatanova, T. G. Markees, K. Bahl, M. A. Brehm, L. D. Shultz, E. A. Kurt-Jones, J. P. Mordes, R. M. Welsh, et al. Type 1 IFN Mediates Cross-Talk between Innate and Adaptive Immunity That Abrogates Transplantation Tolerance J. Immunol., November 15, 2007; 179(10): 6620 - 6629. [Abstract] [Full Text] [PDF] L. K. Selin and M. A. Brehm Frontiers in Nephrology: Heterologous Immunity, T Cell Cross-Reactivity, and Alloreactivity J. Am. Soc. Nephrol., August 1, 2007; 18(8): 2268 - 2277. [Abstract] [Full Text] [PDF]

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