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S Bright

Publications and source records attributed to S Bright.

14 recordsLinked to original sources
PubMed1991

From laboratory to clinic: the development of an immunological reagent.

Access to a wide range of high quality and increasingly sophisticated reagents and equipment has underpinned the great surge of knowledge in basic immunology and the growing interest in clinical immunointervention. In this article, the first in an occasional series on immunological research and development in industry, Sue Bright and colleagues outline the key steps in a development programme to take a humanized monoclonal antibody into the clinic. The procedures involved in developing such reagents, particularly for clinical use, are long and require considerable ingenuity and scientific creativity.

Adenocarcinoma↗
PubMed1983

Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement.

Graft-versus-host disease is one of the major problems in clinical bone marrow transplantation. Many experiments in animals have shown that it could be greatly reduced if mature T lymphocytes were removed from the donor marrow. Here we describe a new rat monoclonal antibody, CAMPATH 1, which is suitable for depleting lymphocytes from human marrow grafts. CAMPATH 1 is an IgM that fixes human complement. It binds to both T and B lymphocytes and some monocytes but not to other hemopoietic cells. When peripheral blood mononuclear cells were treated with CAMPATH 1 and complement, more than 99% of lymphocytes were killed and viable T cells could no longer be detected. Under these conditions, in vitro multipotential erythroid and myeloid colony-forming cells were unaffected. As well as being used for in vitro treatment of bone marrow to remove T cells, CAMPATH 1 could potentially be applied to other experimental and clinical situations where depletion of lymphoid cells is required, including serotherapy to achieve immunosuppression for organ transplants or to treat lymphocytic leukemias.

Antibodies, Monoclonal↗
PubMed1981

Studies on the role of HLA-DR in macrophage-T cell interactions.

The purpose of this paper is to illustrate the difficulties we have encountered in attempting to analyse the role of HLA-DR in the antigen-dependent co-operation between macrophages and T cells which leads to a T-cell proliferative response. We have adopted the two most commonly used approaches; attempted inhibition by anti-HLA-DR antisera and study of co-operation between cells of unrelated individuals, and have found both methods unsatisfactory. With the first method we found that anti-HLA antisera could inhibit proliferative responses in a non-specific manner. Both anti-HLA-A, B and anti-HLA-DR antisera could inhibit and this inhibition was largely Fc-dependent. Using pepsin-digested antisera we have no evidence for a unique role for HLA-DR in these proliferative responses. The second method, study of co-operation between cells of unrelated individuals, proved extremely difficult to analyse because of the background allogeneic reaction. Whether cells of two individuals appeared to co-operate to give an antigen-specific response depended on the number of cells used and the calculations applied to the data. However, it was clearly possible to demonstrate co-operation between DR different individuals.

Antigen-Antibody Reactions↗
PubMed1978

Hypoxic ventilatory responses during thiopentone sedation and anaesthesia in man.

We have assessed the impact of thiopentone on the hypoxic ventilatory reflex, and on the responses to carbon dioxide and doxapram. Thiopentone sedation did not detectably alter any of these aspects of ventilatory control. Thiopentone anaesthesia reduced ventilation and the ventilatory responses to hypoxia, carbon dioxide and doxapram, all approximately in paralle. We conclude that, in contrast to halothane, thiopentone does not selectively reduce the ventilatory response to hypoxia. During light thiopentone anaesthesia, a reasonably brisk hypoxic response is present.

Adolescent↗
PubMed1978

The detection of alloantibodies to subpopulations of human lymphocytes: an adaptation of the indirect anti-immunoglobulin rosetting reaction (IARR).

An indirect anti-immunoglobulin rosetting reaction (IARR) can be successfully used to detect alloantibodies to human lymphocytes. In this paper we describe an adaptation of the IARR which allows detection of alloantibodies to human lymphocyte subpopulations. Fluorescein labelled sheep red cells, as a T cell marker, are incorporated into the rosetting reactions and by looking for rosettes with two indicator cell types, sheep and ox, one can determine if the alloantibodies are reacting with T cells or non-T cells. This type of assay is more sensitive than a standard cytotoxic test and can detect non-cytotoxic antibodies. The results show that this rosetting assay with two types of indicator cell can be useful in the study of pregnancy anisera, particularly those that are thought to contain reactivity directed solely against non-T cells. These antisera probably recognise the human DR antigens which are thought to be equivalent to the rodent Ia antigens.

Animals↗
PubMed1977

An indirect anti-immunoglobulin rosetting reaction to detect alloantibodies to human lymphocytes.

A test is reported which detects alloantibody, absorbed onto the surface of human lymphocytes from multiparous antisera, by means of a red cell rosette assay. The red cells, trypsinised ox, are coupled with anti-immunoglobulin using chromic chloride. The antiglobulin used is rabbit anti-human IgG (Fc), chosen to avoid reaction with the surface immunoglobulin naturally present on human B lymphocytes. The reaction is termed the Indirect Anti-immunoglobulin Rosetting Reaction (IARR). The IARR is shown to be specific in the following ways: anti-immunoglobulin coupled ox cells do not react with normal human lymphocytes nor with lymphocytes treated with non-reactive serum. Red cells coupled with normal rabbit IgG do not react with normal or alloantibody coated lymphocytes. Multiparous sera (reactive with other individuals) do not react with cells of the serum donor in the IARR. Finally, the coupled red cells do not usually react with lymphocytes which have absorbed immune complexes onto their Fc receptors. The IARR is shown to be more sensitive than a standard cytotoxic test for detection of alloantibody. Several possible applications of the IARR are discussed.

Isoantibodies↗
PubMed1977

Relationship between the HLA associated specifities 4a and 4b and the lymphocyte C3 receptor.

Contrary to previous reports, we have obtained no evidence that 4a and 4b antisera specifically inhibit C3 rosette formation by human lymphocytes. Pretreatment of lymphocytes with various whole 4a and 4b antisera resulted in partial inhibition which was often nonsepcific. Ultracentrifugation of the sera to remove immune complexes removed C3 rosette inhibitory activity although specific cytotoxic activity remained. It is probable that immune complexes in antisera will have fixed C3 which will have been converted to C3d and so be able to block the C3d receptor. This is the receptor mainly measured in these and in the previous experiments.

Complement C3↗
PubMed1976

Products of the major histocompatibility complex and their relationship to the immune response.

The genes of the major histocompatibility complex were first known for the part they played in transplant rejection. Recently, however, it has become clear that the products of that region have an important part to play in the control of the immune response, through their effects both on cooperative and on aggressive interactions between cells. It is now possible to guess at the mechanisms which may underly the association of some major histocompatibility antigens with disease.

Alleles↗
PubMed1976

Second locus HL-A antigens and 4a or 4b.

A panel of over 100 individuals was tested against several 4a and 4b antisera. A 4a/4b type was assigned to each individual on the basis of overall reactions with each group of sera. It was felt that because 4a and 4b antisera rarely give identical reaction patterns the use of several sera in each group gave a better definition of the specificities. The relationship between each second locus HL-A specificity and 4a or 4b was assessed. Most of the "narrower" antigens showed complete inclusion within one group but there were some anomalies. Associations of these specificities were analysed further by absorption experiments. 4a and 4b antisera were able to define differences in some second locus specificities which were not picked up by the narrower antisera. It seems likely that 4a and 4b represent a separate public site on the HL-A gene product which is multifactorial. For a full description of the antigens all factors should be stated as there is not an invariant association between components.

Cytotoxicity Tests, Immunologic↗
PubMed1976

The antigens 4a and 4b in rhesus monkeys and stumptailed macaques.

Small panels of rhesus and stumptailed macaques were tested in a cytotoxic assay against human and chimpanzee 4a and 4b alloantisera. The human antisera were also absorbed by macaque platelets and the effect on the serum titer against human cells considered. Results of both types of testing conclusively demonstrated the presence of 4a- and 4b-like antigens on the cells of these two macaque species. Although the frequencies of both specificities were different from those observed for man and chimpanzee, they showed an alternative distribution in the monkey populations as they do in the highest primates.

Animals↗