| First Author | Brehm MA | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 2 | Pages | 819-26 |
| PubMed ID | 16973964 | Mgi Jnum | J:144007 |
| Mgi Id | MGI:3829582 | Doi | 10.1182/blood-2006-03-008219 |
| Citation | Brehm MA, et al. (2007) Rapid quantification of naive alloreactive T cells by TNF-alpha production and correlation with allograft rejection in mice. Blood 109(2):819-26 |
| abstractText | 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. |
