Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an IL-4/STAT6 pathway. Export

@article{citeulike:3432064, abstract = {Graft rejection has been defined as the mirror image of graft-versus-host disease, which is biologically characterized primarily as a Th1-type process. As such, we reasoned that graft rejection would represent a Th1 response amenable to Th2 modulation. Indeed, adoptive transfer of host Th1-type cells mediated rejection of fully MHC-disparate murine bone marrow allografts more effectively than host Th2-type cells. Furthermore, STAT1-deficient host T cells did not differentiate into Th1-type cells in vivo and failed to mediate rejection. We next hypothesized that donor Th2 cell allograft augmentation would prevent rejection by modulation of the host Th1/Th2 balance. In the setting of donor Th2 cell therapy, host-anti-donor allospecific T cells acquired Th2 polarity, persisted post-transplant, and did not mediate rejection. Abrogation of rejection required donor Th2 cell IL-4 secretion and host T cell STAT6 signaling. In conclusion, T cell-mediated marrow graft rejection primarily resembles a Th1-type process that can be abrogated by donor Th2 cell therapy that promotes engraftment through a novel mechanism whereby cytokine polarization is transferred to host T cells.}, author = {Mariotti, Jacopo and Foley, Jason and Ryan, Kaitlyn and Buxhoeveden, Nicole and Kapoor, Veena and Amarnath, Shoba and Fowler, Daniel H H.}, citeulike-article-id = {3432064}, citeulike-linkout-0 = {http://dx.doi.org/10.1182/blood-2008-05-154278}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18625883}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18625883}, day = {14}, doi = {10.1182/blood-2008-05-154278}, issn = {1528-0020}, journal = {Blood}, keywords = {feedback, graft, hvg, il4, polarization, rejection, stat6, superlist, th1, th2, thelist}, month = {July}, posted-at = {2008-10-21 04:18:06}, priority = {2}, title = {Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an IL-4/STAT6 pathway.}, url = {http://dx.doi.org/10.1182/blood-2008-05-154278}, year = {2008} }

TY - JOUR ID - citeulike:3432064 L3 - citeulike-article-id:3432064 N2 - Graft rejection has been defined as the mirror image of graft-versus-host disease, which is biologically characterized primarily as a Th1-type process. As such, we reasoned that graft rejection would represent a Th1 response amenable to Th2 modulation. Indeed, adoptive transfer of host Th1-type cells mediated rejection of fully MHC-disparate murine bone marrow allografts more effectively than host Th2-type cells. Furthermore, STAT1-deficient host T cells did not differentiate into Th1-type cells in vivo and failed to mediate rejection. We next hypothesized that donor Th2 cell allograft augmentation would prevent rejection by modulation of the host Th1/Th2 balance. In the setting of donor Th2 cell therapy, host-anti-donor allospecific T cells acquired Th2 polarity, persisted post-transplant, and did not mediate rejection. Abrogation of rejection required donor Th2 cell IL-4 secretion and host T cell STAT6 signaling. In conclusion, T cell-mediated marrow graft rejection primarily resembles a Th1-type process that can be abrogated by donor Th2 cell therapy that promotes engraftment through a novel mechanism whereby cytokine polarization is transferred to host T cells. JF - Blood SN - 1528-0020 TI - Graft rejection as a Th1-type process amenable to regulation by donor Th2-type cells through an IL-4/STAT6 pathway. KW - feedback KW - graft KW - hvg KW - il4 KW - polarization KW - rejection KW - stat6 KW - superlist KW - th1 KW - th2 KW - thelist AU - Mariotti, Jacopo AU - Foley, Jason AU - Ryan, Kaitlyn AU - Buxhoeveden, Nicole AU - Kapoor, Veena AU - Amarnath, Shoba AU - Fowler, Daniel H PY - 2008/07/14/ UR - http://dx.doi.org/10.1182/blood-2008-05-154278 ER -