Human vascular endothelial cells favor clonal expansion of unusual alloreactive CTL. Export

@article{citeulike:1688834, abstract = {We have shown previously that cultured HUVEC or mixtures of endothelial cells (EC) and B lymphoblastoid cells (BLC) induce the differentiation of purified CD8+ PBL into allospecific, class I MHC-restricted CTL that lyse EC, but not BLC autologous to EC. Furthermore, these EC-selective CTL lines secrete little IFN-gamma after target cell contact. In the present study, we have analyzed these polyclonal populations at a single cell level by cloning at limiting dilution and propagating the resulting CTL clones in the absence of EC. Phenotypically stable, alloreactive EC-selective CTL preferentially emerge from cocultures in which EC or EC + BLC are the initial stimulating cell types compared with cocultures stimulated by BLC alone (p = 0.005). Compared with BLC-stimulated CTL, EC-stimulated CTL clones often fail to secrete IFN-gamma after target cell contact (p = 0.0006) and constitutively express CD40 ligand (CD40L) at rest (p = 0.0006). The absence of IFN-gamma secretion does not result from a switch to IL-4 secretion. The expression of CD40L inversely correlates with the secretion of IFN-gamma after target cell contact (p = 0.0001), but correlations of CD40L expression and failure to secrete IFN-gamma with EC-selective killing did not reach statistical significance. We conclude that in a microenvironment in which allogeneic EC are in close contact with infiltrating CD8+ T cells, such as within a graft arterial intima, CTL subsets may emerge that display EC selectivity or express CD40L and secrete little IFN-gamma after Ag contact.}, address = {Program in Molecular Cardiobiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.}, author = {Biedermann, B. C. and Pober, J. S.}, citeulike-article-id = {1688834}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/10358144}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=10358144}, day = {15}, issn = {0022-1767}, journal = {J Immunol}, keywords = {alloreactive, cd40l, ctl, huvec, rep}, month = {June}, number = {12}, pages = {7022--7030}, posted-at = {2007-09-24 09:36:26}, priority = {2}, title = {Human vascular endothelial cells favor clonal expansion of unusual alloreactive CTL.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/10358144}, volume = {162}, year = {1999} }

TY - JOUR ID - citeulike:1688834 L3 - citeulike-article-id:1688834 N2 - We have shown previously that cultured HUVEC or mixtures of endothelial cells (EC) and B lymphoblastoid cells (BLC) induce the differentiation of purified CD8+ PBL into allospecific, class I MHC-restricted CTL that lyse EC, but not BLC autologous to EC. Furthermore, these EC-selective CTL lines secrete little IFN-gamma after target cell contact. In the present study, we have analyzed these polyclonal populations at a single cell level by cloning at limiting dilution and propagating the resulting CTL clones in the absence of EC. Phenotypically stable, alloreactive EC-selective CTL preferentially emerge from cocultures in which EC or EC + BLC are the initial stimulating cell types compared with cocultures stimulated by BLC alone (p = 0.005). Compared with BLC-stimulated CTL, EC-stimulated CTL clones often fail to secrete IFN-gamma after target cell contact (p = 0.0006) and constitutively express CD40 ligand (CD40L) at rest (p = 0.0006). The absence of IFN-gamma secretion does not result from a switch to IL-4 secretion. The expression of CD40L inversely correlates with the secretion of IFN-gamma after target cell contact (p = 0.0001), but correlations of CD40L expression and failure to secrete IFN-gamma with EC-selective killing did not reach statistical significance. We conclude that in a microenvironment in which allogeneic EC are in close contact with infiltrating CD8+ T cells, such as within a graft arterial intima, CTL subsets may emerge that display EC selectivity or express CD40L and secrete little IFN-gamma after Ag contact. IS - 12 JF - J Immunol SN - 0022-1767 AD - Program in Molecular Cardiobiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA. EP - 7030 TI - Human vascular endothelial cells favor clonal expansion of unusual alloreactive CTL. VL - 162 SP - 7022 KW - alloreactive KW - cd40l KW - ctl KW - huvec KW - rep AU - Biedermann, BC AU - Pober, JS PY - 1999/06/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/10358144 ER -