Learn More
Although certain chemokines and their receptors guide homeostatic recirculation of T cells and others promote recruitment of activated T cells to inflammatory sites, little is known of the mechanisms underlying a third function, migration of Foxp3(+) regulatory T (T reg) cells to sites where they maintain unresponsiveness. We studied how T reg cells are(More)
Foxp3(+) T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3(+) Tregs express multiple histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression, and protein function. Pan-HDAC inhibitors developed for oncologic(More)
Histone/protein deacetylases (HDACs) regulate chromatin remodeling and gene expression as well as the functions of more than 50 transcription factors and nonhistone proteins. We found that administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the production and suppressive function of regulatory T cells (T(reg)(More)
Although almost every known chemokine and chemokine receptor is expressed at some stage during development of allograft rejection, mechanistic studies indicate that the actual key effector mechanisms are rather few. Thus, in vivo studies have alleviated concerns regarding possible biological redundancy and the pleiotropic effects of these molecules, and(More)
Binding of the TNF family member, B cell activating factor (BAFF), to its receptor (BAFF-R, TNFRSF13C) is required for generation and maintenance of mature B cells, but there are no data as to any role for the BAFF/BAFF-R pathway in T cell functions. We report that the binding of BAFF to BAFF-R expressed by a subset of primarily CD4(+) T cells costimulates(More)
OBJECTIVE This study was designed to better understand genetic variation in the cytochrome P450 (CYP) gene CYP1A2 and its impact on CYP1A2 activity in Chinese subjects. METHODS CYP1A2 genetic polymorphisms were screened by direct sequencing in 27 selected Chinese subjects. Plasma 1,7-dimethylxanthine/caffeine ratios 5 hours after a 100-mg caffeine(More)
The B7 homolog B7-H3 is important for the regulation of immune responses though its functions in vivo are controversial. We report the first clinical and experimental data concerning expression and function of B7-H3 in alloresponses. Immunohistological and molecular analyses showed B7-H3 expression by cells mediating rejection of human and mouse allografts.(More)
The recently identified CD28 homolog and costimulatory molecule programmed death-1 (PD-1) and its ligands, PD-L1 and PD-L2, which are homologs of B7, constitute an inhibitory regulatory pathway of potential therapeutic use in immune-mediated diseases. We examined the expression and functions of PD-1 and its ligands in experimental cardiac allograft(More)
Although fully MHC-mismatched murine cardiac allografts are rapidly rejected, allografts mismatched at only MHC class I or class II alleles survive long term; the immunologic basis for the long-term survival of MHC class I- or II-mismatched allografts is unknown. We examined the roles of two recently described inhibitory receptors, B and T lymphocyte(More)
The binding of herpesvirus entry mediator (HVEM) to B and T lymphocyte attenuator (BTLA) is known to activate an inhibitory signaling cascade in effector T (Teff) cells, but we now report that the HVEM-BTLA pathway is also important to the suppressive function of regulatory T cells (Tregs). Although naive T cells up-regulated BTLA upon TCR activation, Treg(More)