A New T-Cell Receptor Transgenic Model of the CD4+ Direct Pathway: Level of Priming Determines Acute Versus Chronic Rejection

Abstract

Rejection of a graft by the direct CD4 pathway is determined by graft susceptibility to rejection, as well as the degree of T-cell priming caused by the graft. Grafts that are not acutely rejected can develop transplant vasculopathy mediated by the direct CD4 T cells.

Heparan sulfate mimetic PG545-mediated antilymphoma effects require TLR9-dependent NK cell activation

“…IRES.GFP (57) in front of the ubiquitin promoter of a previously described lentiviral vector (58). Lentiviral particles were packaged in 293T cells using Δ8.9 and pCMV-VSVg and concentrated by centrifugation as described previously (58,59). Murine B cell (A20) and T cell (EL-4) lymphoma cell lines were transduced with lentivirus in the presence of 6 μg/ml Polybrene (Sigma-Aldrich) for 90 minutes during centrifugation at 1,200 at 23°C.…”

Direct and indirect antigen presentation lead to deletion of donor-specific T cells after in utero hematopoietic cell transplantation in mice

“…18 Although we previously showed, using an in vivo MLR, that allospecific T cells are decreased, 8 this system does not allow us to explore whether direct or indirect antigen presentation is dominant at various times after transplantation, or to study whether antigenspecific Tregs are induced. We therefore used TCR-Tg systems in which host CD4 T cells respond to a BALB/c antigen via direct or indirect presentation and examined deletion and Treg induction in 27 or TCR75 males 28 and transplanted the resulting fetuses with BALB/c fetal liver cells on E14.5 (Figure 2A d presented on B6 MHC class II (indirect pathway). Because the males were heterozygous for the TCR transgene, half of the pups in each litter were expected to be TCR transgenic and half were expected to be wild type.…”

Heparan sulfate, an endogenous TLR4 agonist, promotes acute GVHD after allogeneic stem cell transplantation

“…22 BALB/c recipients of C57BL/6 HSCTs (10 7 TCD-C57BL/6 BM and 10 6 C57BL/6 LN cells) were intravenously injected with 2 ϫ 10 6 CFSE-labeled LN cells 14 days after transplant. Three days later, mice were killed, their livers were harvested, and intrahepatic lymphocytes were purified after mechanical disruption on a discontinuous Ficoll (SigmaAldrich) gradient.…”

“…Intracellular IFN-␥ staining was performed as described previously. 22 For in vivo BrdU labeling, mice were injected with 50 g of BrdU/g intraperitoneally 1 hour before analysis. Collection of flow cytometric data was acquired using an FACSCanto flow cytometer (BD Biosciences), and events were analyzed using FlowJo Version 9.3 software (TreeStar).…”