Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice
Authors
Brehm, Michael A.Mangada, Julie A.
Markees, Thomas G.
Pearson, Todd
Daniels, Keith A.
Thornley, Thomas B.
Welsh, Raymond M.
Rossini, Aldo A.
Greiner, Dale L.
Document Type
Journal ArticlePublication Date
2006-09-16Keywords
AnimalsGraft Rejection
Humans
Interferon Type II
Leukocytes
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred CBA
Mice, Transgenic
Skin Transplantation
T-Lymphocytes
*Transplantation Tolerance
Tumor Necrosis Factor-alpha
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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-alpha but not IFN-gamma. Naive alloreactive T cells were identified by the production of TNF-alpha after a 5-hour in vitro stimulation with alloantigen and were distinguished from effector/memory alloreactive T cells by the inability to produce IFN-gamma. Moreover, naive alloreactive T cells were not detected in mice tolerized against specific alloantigens. The frequency of TNF-alpha-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-alpha 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.Source
Blood. 2007 Jan 15;109(2):819-26. Epub 2006 Sep 14. Link to article on publisher's siteDOI
10.1182/blood-2006-03-008219Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39923PubMed ID
16973964Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1182/blood-2006-03-008219