Protection of xenografts by a combination of immunoisolation and a single dose of anti-CD4 antibody.

Immunoisolation is the separation of transplanted cells from cells of the immune system using a semipermeable membrane. Using one such immunoisolation capsule-the TheraCyte device-we have assessed the survival of encapsulated xenogeneic tissue in vivo as well as the contribution of CD4+ve T cells to encapsulated xenograft rejection. The foreign body reaction to the TheraCyte capsule in vivo was assessed by transplanting empty capsules into normal mice. These capsules elicit a foreign body response by the host animal. Encapsulated CHO, NIT-1, and PK-15 cells were placed in culture and in immunodeficient mice to investigate their growth characteristics in the TheraCyte device. These cell lines survive both in culture and in immunodeficient SCID mice. Xenogeneic PK cells were also transplanted into normal C57BL/6 mice. These cells do not survive in normal mice despite the absence of direct contact between infiltrating and encapsulated cells. In addition, the survival of encapsulated cells in mice treated with a single dose of anti-CD4 antibody was examined. This was assessed using two systems: 1) histological analysis of capsule sections; 2) a quantitative luciferase reporter system using PK cells transfected to express luciferase. In both cases, anti-CD4 antibody contributed to prolonged encapsulated xenogeneic cell survival. Encapsulated xenogeneic cells survive in immunodeficient mice but not normal mice. Treatment of normal mice with anti-CD4 antibody results in prolonged survival of xenogeneic cells that can be measured using a luciferase reporter system. These results highlight the contribution of CD4+ve T cells to encapsulated xenograft rejection.

Local secretion of a chimeric anti-CD4 antibody protects against graft rejection in the NOD mouse.

BACKGROUND: Engineering a graft to secrete its own immunosuppressive antibodies may minimize the risks associated with current high dose systemic immunosuppression. METHODS AND RESULTS: A beta cell insulinoma cell line (NIT-1) was transfected with genes encoding a chimeric anti-CD4 antibody. The NIT-1 cells secreted functional chimeric anti-CD4 antibody that bound to the CD4 molecule on mouse thymocytes and inhibited in vitro proliferation of CD4+ve T cells. Both test and control transfected cell lines grew at a similar rate in immunodeficient mice. In immunocompetent NOD mice, NIT-1 cells are normally rejected by a cellular immune response against the SV40 T antigen. Although control transfected NIT-1 cells were rapidly rejected by NOD mice, anti-CD4 secreting NIT-1 cells grew significantly better and were able to form tumors at the site of injection. CONCLUSIONS: The local secretion of chimeric anti-CD4 antibody from transfected cells can contribute to graft survival in our transplantation model.

Lyell's syndrome on a burns unit.

Two cases of Lyell's syndrome (toxic epidermal necrolysis) managed on a burn unit are presented. The various methods of management are discussed, and the arguments for treating this life-threatening condition on an intensive care burn unit are analysed.

Bullous pemphigoid and primary biliary cirrhosis.

The occurrence of multiple autoimmune conditions in an individual and in families is well known. We wish to report the simultaneous occurrence of bullous pemphigoid and primary biliary cirrhosis in an individual who also suffered from vitiligo. The association adds to the documentation of bullous pemphigoid co-existing with other autoimmune disorders.

HL-A antigens in patients with guttate psoriasis.

Tissue typing was performed on lymphocytes of sixty-two patients with guttate psoriasis, in forty-four of whom this was the first manifestations of the disease. In 84% of cases, the guttate psoriasis was preceded by a clinical infection. A highly significant excess of antigen W17 (HLA-BW17) was found in patients when compared with healthy population. In common with some other studies antigens HL-A13 (HLA-B13), W15 (HLA-BW15) and W21 (HLA-BW21) were found in excess but these became non-significant after correction for the number of antigens studied. 68% of patients who had guttate psoriasis de novo, subsequently developed persistent plaque psoriasis.

Prurigo nodularis and gluten enteropathy.

Two cases of prurigo nodularis are described. Each is considered to have a gluten sensitive enteropathy. This association may be one facet of prurigo nodularis.

A new formulation of 0.1% hydrocortisone cream with vasoconstrictor activity and clinical effectiveness.

A new formulation of hydrocortisone with vasoconstrictor activity has been shown to be effective clinically and was more effective in a 0.1% concentration than 1.0% Hydrocortisone Cream BPC. Its use should obviate the adverse effects of fluorinated steroids.