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Biomedical subjects

A G Dalgleish

Publications and source records attributed to A G Dalgleish.

At least 19 recordsLinked to original sources
PubMed1992

T-cell receptor variable gene products and early HIV-1 infection.

To assess the hypothesis that the human immunodeficiency virus (HIV) might mimic major histocompatibility complex (MHC) allodeterminants and interact with T-cell receptors (TCRs) of alloreactive T-cells, we have done a preliminary analysis of the range of alpha beta TCR gene products in 16 HIV-1-seropositive individuals with normal CD4 counts and in 16 healthy HIV-1-negative controls. Using a panel of monoclonal antibodies with a two-colour direct immunofluorescence method, we found a significant increase in the expression of the V beta 5.3 subfamily in the HIV-positive patient group compared with controls (p less than 0.01). Selected increase in expression of V beta sequences has been described in various autoimmune conditions and our findings raise the possibility that the immunopathological damage from HIV infection may be due to the induction of autoreactivity. If HIV does mimic MHC II, the normal immune response to the virus could represent an autoimmune process similar to graft-versus-host disease.

Gene Expression↗
PubMed1992

Neopterin concentrations in serum and cerebrospinal fluid in HTLV-I infected individuals.

The concentration of neopterin was measured in serum samples taken from individuals infected with HTLV-I: 5 from asymptomatic individuals, 1 from a patient with adult T-cell leukaemia and 30 from patients with tropical spastic paraparesis (TSP). In addition, cerebrospinal fluid (CSF) was available from 22 of the TSP patients and neopterin concentrations were determined in these. Elevated levels of neopterin were found in only 3 of the 36 HTLV-I-positive serum samples, all from TSP patients, but significantly elevated neopterin levels were observed in 12 of the 22 CSF samples. The localisation of the elevated neopterin concentrations to the CSF of patients with TSP suggests a marked degree of activation of the cell-mediated immune system intrathecally. This provides further evidence in favour of powerful immune mechanisms operating centrally in the pathogenesis of TSP.

Biopterins↗
PubMed1992

Immunotherapy of AIDS.

The immunotherapy of AIDS encompasses a broad range of therapeutic possibilities. A number of stimulating and immunomodulating agents have been tried without any overt success. More recently, passive immunotherapy of AIDS using donated plasma and active therapeutic vaccine procedures have been reported. A number of clinical and laboratory observations together with preliminary results of clinical trials suggest that post-infection vaccines may be able to delay progression to disease in some individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Inhibitory activity of HIV envelope gp120 dominates over its antigenicity for human T cells.

HIV-1 envelope glycoprotein (gp120), as a CD4-binding reactant, has been shown to inhibit in its native form human T cell responses to several antigens. Here we show that gp120 in soluble form also inhibits activation of a specific human T cell line that responds to gp120-pulsed autologous antigen-presenting cells. In addition the inhibitory property of gp120 for antigen-driven T cell proliferation depends upon its ability to bind CD4 and is lost when CD4-binding capacity is abolished by denaturation, or blocked by complexing with soluble CD4 or with polyclonal antibodies. In contrast, antigenicity of denatured or complexed gp120 for specific human T cells is preserved. Similar effects are also observed with another CD4-binding reactant (i.e. anti-Leu 3a MoAb), which stimulates and/or inhibits human T cells specific for mouse immunoglobulins depending on native or denatured conformation.

Antibodies, Monoclonal↗
PubMed1992

HIV-induced deletion of antigen-specific T cell function is MHC restricted.

When antigen-specific T cells are pulsed by antigen-presenting cells (APC) in the presence of HIV they are functionally deleted following subsequent exposure to syngeneic APC in the absence of HIV. Recombinant soluble HIV envelope (gp120) is able to induce a similar effect which, unlike that induced by HIV, is reversible. Neither HIV nor gp120 affect the ability to respond to IL-2. Thus it is only antigen-specific responses involving the T cell receptor pathways and CD4/MHC class II interaction that appear to be inhibited by HIV-1 and gp120. Furthermore, the functional impairment caused by HIV-1 is specific to the T cells that respond to the antigen in co-culture with HIV, as there is no apparent effect on 'bystander'-activated T cells specific for another antigen. Antigen-specific T cell lines may be deleted by a signalling mechanism which involves molecules other than gp120/CD4 but still requires MHC class II restriction.

Animals↗
PubMed1992

HTLV-I infection and neurological disease in Rio de Janeiro.

Fifty patients with chronic neurological diseases attending a clinic in Rio de Janeiro, Brazil, were examined for evidence of HTLV-I infection. Fifteen of 27 with progressive paraparesis of obscure origin had antibodies to HTLV-I in high titre in their serum samples, and 10 of 13 studied had antibodies in their cerebrospinal fluid. The clinical features of the antibody positive patients were similar to those of patients with HTLV-I associated myelopathy from other countries except that half of the Brazilian patients were white. Seven patients had multiple sclerosis and one of these had antibodies to HTLV-I in the serum. None of the eight patients with motor neuron disease and four with polymyositis had HTLV-I antibodies in their serum samples.

Africa↗
PubMed1992

The pathogenesis of AIDS: classical and alternative views.

As HIV readily kills CD4 cells in vitro it has been widely assumed that this would account for the declining CD4 counts in vivo. A growing number of reports suggest that the pathogenesis of AIDS is considerably more complex than had been thought. A number of indirect mechanisms for CD4 cell death have been proposed. In this review of alternative theories which could explain the features of AIDS, autoreactivity and genetic restriction to the development of disease are considered the most important. In addition it is suggested that if HIV is able to mimic MHC antigens on the surface of antigen presenting cells then this could stimulate 'allo reactive' T lymphocytes, which would explain the marked similarity of HIV infection to chronic graft versus host disease.

Acquired Immunodeficiency Syndrome↗
PubMed1991

A proposed molecular model for the carboxy terminus of HIV-1 gp120 showing structural features consistent with the presence of a T-cell alloepitope.

A computer graphics molecular model of the C terminus of gp120 of HIV has been constructed using predicted secondary structure based on homologies with proteins for which X-ray crystallographic data have been published. The model shows sequences known to be important in CD4 binding in close proximity to regions with a high probability of forming alpha helical and beta strand motifs. The orientation adopted by these domains approximates to the known 3D structure of HLA-A2 alpha 2 chain without constraints based on HLA-A2 as a template being introduced. The model may therefore represent an energetically favourable conformation for a part of gp120 which mimics the binding domain for the T-cell receptor on MHC molecules. Recognition of gp120 as an alloepitope in high affinity association with CD4 would explain many of the sequelae of acquired immune deficiency on HIV infection.

Amino Acid Sequence↗
PubMed1991

Vascular endothelium: a potential role in HIV infection and the pathogenesis of Kaposi's sarcoma: observations and speculations.

Kaposi's sarcoma (KS) has become a source of interest in recent years primarily for its strong association with the acquired immune deficiency syndrome (AIDS). Endothelial cells (EC) are central to inflammation and can regulate coagulation and leucocyte emigration and may be central to the development of the disease. As they are also capable of being infected by HIV in vivo, this infection may contribute to the immunosuppressive effects of HIV seen in AIDS. Recent work has shed new light on the mechanisms involved in EC proliferation. The aim of this article is to review such evidence implicating EC in the development of KS. Additionally, hypotheses will be put forward to explain the mechanism of the vascular proliferation in KS and the possible role of EC in HIV infection. There is therefore enormous potential for the therapeutic targeting of endothelium to control these diseases.

Endothelium, Vascular↗
PubMed1991

HIV types and testing.

The past year has seen the discovery of new isolates which do not readily fit into the established categories HIV-1, HIV-2 and SIV, as well as the availability of new assays including the use of the polymerase chain reaction. New combination enzyme-linked immunosorbent assays can detect viruses from two or more groups where specific enzyme-linked immunosorbent assays have been developed using peptides and monoclonal antibodies.

Female↗