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Biomedical subjects

D Gay

Publications and source records attributed to D Gay.

16 recordsLinked to original sources
PubMed1991

Blood-brain barrier damage in acute multiple sclerosis plaques. An immunocytological study.

To investigate blood-barrier leakage of plasma proteins in acute plaques of multiple sclerosis (MS) the authors used immunocytological methods to examine frozen tissue removed at autopsy from recently active cases. Annular patterns of protein-rich leakage were seen which may help to elucidate the patterns observed using gadolinium-enhanced nuclear magnetic resonance imaging. Vessel wall damage was found in all acute plaques examined and this was associated with the intramural deposition of complement on smooth muscle components and with an infiltration of HLA-DR +ve macrophages. In addition, all acute cases examined had small plaques which contained particulate material within macrophages and astrocytes, on which complement and immunoglobulins colocated. Attempts to find similar material in cases of chronic MS, subacute sclerosing panencephalitis and in perivenous encephalomyelitis were unsuccessful. These results suggest that the inflammatory changes in early MS plaques may have some specificity which could be related to the antigens whose presence is inferred by the colocation of complement and immunoglobulin on material within activated macrophages and astrocytes.

Acute Disease↗
PubMed1990

Immunological and neuropathological significance of the Virchow-Robin space.

The anatomy of the Virchow-Robin space is reviewed and attention is drawn to its importance as a compartment which is in communication with lymphatic channels of the head and neck and in which local immunological reactions take place. Macrophages in the Virchow-Robin spaces express MHC class II antigens and are well placed to interact with lymphocytes derived from the blood in initiating and promoting immune response to foreign antigens in the brain. The immunological reactions taking place in the Virchow-Robin spaces in encephalitis, multiple sclerosis and human immunodeficiency virus encephalitis are examined for the light they may throw on the pathogenesis of these conditions.

AIDS Dementia Complex↗
PubMed1989

Epitopic analysis by anti-I-Ak monoclonal antibodies of I-Ak-restricted presentation of lysozyme peptides.

Anti-I-A mAb were used as probes of functional epitopes for both the presentation of hen egg lysozyme (HEL) peptides to I-Ak-restricted T cell hybridomas and the direct binding of the HEL (46-61) peptide. When mAb directed to polymorphic regions of I-Ak were used as inhibitors of Ag presentation, several different patterns of inhibition were observed among T cells specific for the same HEL peptide as well as among T cells specific for different fragments of HEL. Although there appears to be a conserved usage of some TCR V beta gene segments among the T cell hybrids specific for the same HEL peptide, no correlation is evident between a single V gene usage and susceptibility to blocking of Ag presentation by a particular anti-I-Ak mAb. Several of the mAb demonstrated T cell "clonotypic blocking" of Ag presentation, whereas others blocked presentation to every T cell hybrid tested, regardless of the peptide specificity. When mAb directed to nonpolymorphic regions of the I-A molecule were tested for their ability to block Ag presentation, little or no inhibition was observed. In addition, Fab' fragments of inhibitory mAb functioned identically to their intact homologous counterparts in their ability to block Ag presentation indicating that "nonspecific" steric hindrance was not playing a major role in the inhibitions observed. When the polymorphic region-directed anti-I-A mAb were tested for their ability to block the direct binding of the lysozyme peptide HEL(46-61) to I-Ak, those mAb that block HEL presentation to all T cell hybrids were found to block the binding of this peptide. However, anti-I-A mAb that demonstrate selective inhibition of T cell hybrid stimulation during Ag presentation, i.e., those directed to polymorphic serologic specificities Ia.15 and Ia.19, do not block the binding of HEL(46-61) to I-Ak. These data indicate that functionally independent epitopes exist on the I-Ak molecule for the binding of antigenic peptides and for interaction with the TCR.

Animals↗
PubMed1988

The T-cell accessory molecule CD4 recognizes a monomorphic determinant on isolated Ia.

The membrane protein CD4 is commonly found on mature T cells specific for antigen in association with class II major histocompatibility complex (MHC; Ia) proteins. This correlation has led to the suggestion that CD4 binds to a monomorphic region of the Ia molecule on the antigen-presenting cell (APC) and functions either by enhancing interaction between the T cell and the APC, or conversely, by transducing negative signals to the T cell. To address this hypothesis, we have made use of sublines from an unusual T hybrid that is class I MHC restricted but also CD4+. By incorporating purified MHC proteins into a planar membrane system, we show that different Ia molecules can greatly enhance the ability of a CD4+ but not a CD4- variant of this class I-restricted T hybrid to respond to isolated class I molecules. T-cell responses can be strongly augmented by the concurrent expression of CD4 on the T cell and any of four different Ia proteins on planar membranes, thus supporting the idea that CD4 binds to a monomorphic region of the Ia molecule and increases the avidity with which the T cell can interact with its target.

Animals↗
PubMed1986

The T cell repertoire may be biased in favor of MHC recognition.

The receptors of two T cell hybridomas that recognize class I and class II major histocompatibility complex (MHC) molecules, respectively, have been compared. In both cases these receptors are hybrid molecules formed as a result of cellular fusion. The receptors contain the same alpha chain, contributed by the tumor cell fusion partner, and related beta chains, contributed by the normal T cell component. Thus, surprisingly, the same alpha chain can contribute to recognition of class I and class II MHC molecules. Moreover, the finding that in two independent examples hybrid receptor molecules created randomly by in vitro cell fusion recognize MHC supports the theory that the T cell repertoire has an intrinsic affinity for MHC.

Antibodies, Monoclonal↗
PubMed1986

Is multiple sclerosis caused by an oral spirochaete?

Evidence of a direct link between chronic sinusitis and multiple sclerosis (MS) prompted examination of the old "spirochaetal hypothesis". This hypothesis has not been shown to be erroneous and a spirochaetal infection of the central nervous system could explain the specific pathological, immunological, and epidemiological features of MS.

Acute Disease↗
PubMed1986

Multiple sclerosis associated with sinusitis: case-controlled study in general practice.

In an analysis of general practice records the rate of chronic sinusitis was significantly greater in 92 patients with multiple sclerosis (MS) than in matched controls (p less than 0.0001). MS and chronic sinus infection were also significantly associated in the timing of attacks, in the age at which patients suffered their attacks, and in the seasonal pattern of attacks.

Adolescent↗
PubMed1986

[Testicular function during prolonged corticotherapy].

Prolonged corticosteroid therapy produces a major degree of protein catabolism. Short-term treatment with ACTH or glucocorticoids results, in males, in a fall in plasma testosterone levels. In order to determine the origin of this hypogonadism, the testicular function was investigated in 18 men under prolonged glucocorticoid treatment. The mean plasma testosterone level in men treated for less than 3 months (5.9 +/- 0.8 ng/ml) was not statistically different from that obtained in controls (7.5 +/- 0.5 ng/ml; P greater than 0.05). However, the mean plasma luteinizing hormone level was significantly higher in these patients than in controls (8.2 +/- 1.9 mUl/ml vs 3.6 +/- mUl/ml respectively; P less than 0.001). In patients treated for more than 2 years, the mean plasma testosterone level (3.8 +/- 0.6 ng/ml) was significantly lower than in controls (P less than 0.001), but the mean plasma luteinizing hormone level was normal (5 +/- 1 mUl/ml). Plasma testosterone levels are negatively correlated with the daily dose of glucocorticoid (r = -0.81; P less than 0.001). The free testosterone index was within normal range in 5 of the 9 men under prolonged steroid therapy, near the lower limit of normality in 2 men and definitely low in 2 other men. The gonadotrophin response to the luteinizing hormone releasing hormone was normal, whereas the testicular response to human chorionic gonadotrophin was reduced. These data suggest that prolonged treatment with steroidal anti-inflammatory agents influences both gonadotrophic and testicular function and may be associated with true hypoandrogenism.

Adrenal Cortex Hormones↗
PubMed1986

The major histocompatibility complex-restricted antigen receptor on T cells. IX. Role of accessory molecules in recognition of antigen plus isolated IA.

Antibody inhibition studies were done to determine which molecules on the surface of the T cell hybridomas other than their receptors for antigen plus IAd were involved in interaction with antigen-presenting B cells, with artificial IAd membranes on glass beads, or with anti-receptor antibodies coupled to Sepharose beads. We found that T cell LFA-1 was only involved when B cells were used to present antigen plus IAd, whereas T cell L3T4 was involved in the response of T cells to antigen plus IAd either on cells or in artificial membranes, but not if anti-receptor antibodies were used to stimulate the T cells. From these results we concluded that LFA-1 may be involved in the recognition of a ligand on cells that was not present in artificial membranes, but that L3T4 might interact with a nonpolymorphic portion of class II molecules present in both intact antigen-presenting cells and the antigen-presenting artificial membranes.

Animals↗
PubMed1986

The role of LFA-1 in class II restricted, antigen-specific T-cell responses.

We have studied the role of the murine lymphocyte function associated antigen-1 (LFA-1) in the major histocompatibility complex (MHC)-restricted responses of a panel of T-cell hybridomas to protein antigens. Monoclonal antibodies to LFA-1 showed a differential blocking effect in these responses that correlated with the overall "sensitivity" of a given hybrid to antigen and MHC as defined by other criteria already reported. This result differs completely from similar experiments in the CTL system where all clones regardless of their overall "avidity" for target cells are very sensitive to the blocking effects of anti-LFA-1. Further, we show that no blocking effects are observed in the response of our hybridomas when Class I or Class II transfected fibroblasts or cultured 3T3 fibroblasts are used as synthetic antigen presenting cells and the result is unaltered by preincubation of such cells with interferon-gamma (IFN-gamma).

Animals↗
PubMed1985

The beta 1 domain of the mouse E beta chain is important for restricted antigen presentation to helper T-cell hybridomas.

We have constructed a hybrid E beta gene by replacing the second exon of the Ed beta gene (which encodes the majority of the beta 1 protein domain) with the corresponding exon from the Eb beta gene. The hybrid gene has been introduced into a d haplotype host, the lymphoma beta-cell line A20-2J, and an E alpha E beta dimer composed of the endogenous Ed alpha chain and the product of the hybrid Ed beta/Eb beta gene was immunoprecipitated from extracts of transfected cells with an Ed alpha Eb beta-specific monoclonal antibody. Transfected cells have acquired the ability to present antigen to Ed alpha Eb beta-restricted helper T-cell hybridomas, indicating that the second exon of the gene for the E beta chain encodes sequences required for the restricted recognition of the antigen-presenting cell by the class II-restricted responder T-cell.

Animals↗
PubMedDate not supplied

Functional interaction between human T-cell protein CD4 and the major histocompatibility complex HLA-DR antigen.

Mature T cells segregate phenotypically into one of two classes: those that express the surface glycoprotein CD4, and those that express the glycoprotein CD8. The CD4 molecule is expressed primarily on helper T cells whereas CD8 is found on cytotoxic and suppressor cells. A more stringent association exists, however, between these T-cell subsets and the major histocompatibility complex (MHC) gene products recognized by their T-cell receptors (TCRs). CD8+ lymphocytes interact with targets expressing class I MHC gene products, whereas CD4+ cells interact with class II MHC-bearing targets. To explain this association, it has been proposed that these 'accessory' molecules bind to monomorphic regions of the MHC proteins on the target cell, CD4 to class II and CD8 to class I products. This binding could hold the T cell and its target together, thus improving the probability of the formation of the trimolecular antigen: MHC: TCR complex. Because the TCR on CD4+ cells binds antigen in association with class II MHC, it has been difficult to design experiments to detect the association of CD4 with a class II molecule. To address this issue, we devised a xenogeneic system in which human CD4 complementary DNA was transfected into the murine CD4-, CD8- T-cell hybridoma 3DT-52.5.8, the TCR of which recognizes the murine class I molecule H-2Dd. The murine H-2Dd-bearing target cell line, P815, was cotransfected with human class II HLA-DR alpha, beta and invariant chain cDNAs. Co-culture of the parental T-cell and P815 lines, or of one parental and one transfected line resulted in a low baseline response. In contrast, a substantial increase in response was observed when CD4+ 3DT-52.5.8 cells were co-cultured with HLA-DR+ P815 cells. This result strongly indicates that CD4:HLA-DR binding occurs in this system and that this interaction augments T-cell activation.

Animals↗