Department of Pathology; Department of Medicine, Division of Diabetes
Animals; Graft 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
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.
DOI of Published Version
Blood. 2007 Jan 15;109(2):819-26. Epub 2006 Sep 14. Link to article on publisher's site
Brehm MA, Mangada JA, Markees TG, Pearson T, Daniels KA, Thornley TB, Welsh RM, Rossini AA, Greiner DL. (2006). Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice. Open Access Articles. https://doi.org/10.1182/blood-2006-03-008219. Retrieved from https://escholarship.umassmed.edu/oapubs/273