Biomedical subjects

Eleanor M Bolton

Publications and source records attributed to Eleanor M Bolton.

5 recordsLinked to original sources

PubMed2003

Complementary DNA sequences encoding the rat MHC class II RT1-Bu and RT1-Du alpha and beta chains.

The rat major histocompatibility complex loci RT1-B and RT1-D are equivalent to the human leucocyte antigens HLA-DQ and HLA-DR respectively. Here we describe the complementary DNA (cDNA) sequence encoding the alpha and beta chains of both the RT1-B and RT1-D locus genes of the rat RT1u haplotype. We have found entire sequence identity between five different inbred rat strains of the RT1u haplotype, which differs from previously published, incomplete sequences. This information is of considerable value for experimental studies of transplantation immunity and autoimmune disease.

Animals↗

PubMed2002

Lentiviral vectors for delivery of genes into neonatal and adult ventricular cardiac myocytes in vitro and in vivo.

Vectors based on lentiviruses such as human immunodeficiency virus (HIV) type-1 have many advantages for gene therapy, including the ability to infect non-dividing cells, long-term transgene expression and the absence of induction of an inflammatory/immune response. This study was initiated to determine whether lentiviruses would efficiently transfer genes to both neonatal and adult cardiac cells in culture and, by direct injection, to the heart in vivo. A three-plasmid expression system, including a packaging defective helper construct, a plasmid coding for a heterologous (VSV-G) envelope protein and a vector construct harboring reporter genes - E-GFP (enhanced green fluorescent protein) and puro (puromycin-resistance protein) was used to generate pseudotyped HIV-1 particles by transient transfection of human embryonic kidney 293T cells. We demonstrated efficient gene transfer into neonatal and adult cardiac myocytes in vitro and identified conditions in which virtually 100 % of cultured neonatal and 70 % of adult cardiac myocytes express the reporter gene. Transduction of adult cardiac myocytes with high titre lentiviral vectors did not affect the cell number, morphology or viability compared to untransduced cells. We delivered HIV-1-based vectors to the intact heart by direct injection. Hearts transduced with pseudotyped HIV-1 vectors showed levels of transgene expression comparable to that achieved by adenovirus vectors. This study demonstrates for the first time that lentivirus-based vectors can successfully transduce adult cardiomyocytes both in vitro and in vivo, and opens up the prospect of lentivirus-based vectors becoming an important gene delivery system in the cardiovascular field.

Adult↗

PubMed2002

Stem cell medicine encounters the immune system.

Recent progress in deriving human embryonic stem (hES) cells and defining their capacity to differentiate has inspired hope that they could become a source of replacement cells for damaged or diseased tissues. We review the immunological barriers to transplanting hES cells and consider several potential solutions, including stem-cell banking, modification of the immunogenicity of donor cells and induction of tolerance to the graft. We evaluate the probable efficacy of these approaches with a view to facilitating the use of hES cells in clinical practice.

ABO Blood-Group System↗

PubMed2002

Targeting IL-15 as a therapeutic strategy in organ transplant rejection.

Much effort is currently directed towards generating and evaluating agents that target the individual components of the alloimmune response, with a view to promoting allograft survival accompanied by minimum side effects. Recently, there has been considerable interest in inhibiting individual cytokine/receptor interactions since they are key elements in pathways for differentiation of immune effector cells. This article examines the utility of targeting interactions of interleukin (IL)-15 with its receptor as a strategy for disabling the T-cell activation events following recognition of foreign major and minor histocompatibility antigens. Experimental evidence suggests that interrupting IL-15/IL-15R interaction may be of therapeutic value in preventing allograft rejection.

Animals↗

PubMedDate not supplied

CTLA4-Ig abrogates the anti-globulin response and prolongs cardiac allograft survival after anti-CD2 treatment.

CD2 is expressed on T cells and NK cells and is important in T cell activation, making it a potential target for immune intervention. Here, we report a series of experiments aimed at defining the ability of mAbs directed against the CD2 molecule to prevent cardiac allograft rejection in low and high responder rat strain combinations. Administration of the mouse anti-rat CD2 mAbs OX34 or OX55 around the time of transplantation prolonged survival of fully allogeneic Lewis (RT1l) cardiac allografts in low responder DA (RT1a) recipients (MST 14 days for OX55 and >100 days for OX34). Treatment with OX34 prolonged graft survival in the reciprocal high responder DA to Lewis rat strain combination (MST 19 days) and when combined with CTLA4-Ig resulted in long-term graft survival (MST>100 days). Despite these in vivo effects, OX34 had little effect on in vitro assays of lymphocyte activation. Instead, the ability of OX34 to extend allograft survival correlated with T cell depletion. Administration of OX34 induced a similar degree of CD4 T cell depletion in DA and Lewis recipients, but the CD4 depletion observed was more transient in Lewis recipients. Lewis, but not DA strain rats, developed an anti-murine Ig response. Combined treatment with CTLA4-Ig abolished the anti-globulin response to OX34 in Lewis recipients, prolonged circulation of OX34 and increased the extent and duration of CD4 depletion. We conclude that anti-CD2 treatment effectively prolongs cardiac allograft survival and addition of CTLA4-Ig increases its efficacy by abrogating the production of neutralising antibodies.

Abatacept↗