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A J Quayle

Publications and source records attributed to A J Quayle.

30 records · Page 2Linked to original sources

Peptide recognition, T cell receptor usage and HLA restriction elements of human heat-shock protein (hsp) 60 and mycobacterial 65-kDa hsp-reactive T cell clones from rheumatoid synovial fluid.

A commonly held postulate regarding the etiology of rheumatoid arthritis (RA) is that of antigenic mimicry. Recent interest has focused on the mycobacterial 65-kDa heat-shock protein (hsp) as a putative causal agent. The 65-kDa hsp has over 40% sequence homology with the human hsp 60, and elevated synovial T cell responses to both antigens have been demonstrated in RA and juvenile rheumatoid arthritis patients. Such T cells should, therefore, be specific for shared epitopes on the two antigens. To investigate this, we screened synovial fluid mononuclear cells from two early RA patients with peptides of the 65-kDa hsp which have the greatest homology with the human hsp 60. We also raised a panel of T cell clones from one of the patients with the 65-kDa hsp. The synovial T cell population from both patients and one of the T cell clones recognized a peptide representing the amino-acid sequence 241-255. This clone also responded to the peptide of the equivalent human sequence, and was restricted by HLA-DQ. A second T cell clone recognized an adjacent epitope (amino acid sequence 251-265) which is also highly homologous with the human sequence, but this clone was restricted by HLA-DR. The clones utilized different V beta gene segments but the same D beta and J beta gene elements, and both exhibited specific cytotoxicity against autologous antigen-pulsed macrophages. Our findings, therefore, do not disagree with the postulate that autoimmune disease could possibly be triggered by bacterial epitopes with homology to self protein. However, it is also noted that there are alternative interpretations of this data.

Adult↗

TCR gamma/delta+ cell subsets in the synovial membranes of patients with rheumatoid arthritis and juvenile rheumatoid arthritis.

Using a peroxidase/anti-peroxidase immunohistochemical staining method, we examined sections of inflammatory synovial membranes from 13 patients with juvenile rheumatoid arthritis (JRA) and 11 with rheumatoid arthritis (RA). The relative numbers of TCR gamma/delta+ cells and the proportions of V delta 1+ and V delta 2+ subsets were recorded in the areas of the membranes most heavily infiltrated by CD3+ cells. In the JRA group, the majority (8/13) of the membranes had TCR gamma/delta+ cells which contributed between 5 and less than 10% of the total number of CD3+ cells. In the RA synovial membranes examined, 5/11 samples had between 5 and 10% TCR gamma/delta+ cells, but in another 5 TCR gamma/delta+ cells contributed to between 10 and 20% of CD3+ cells. No significant difference was noted between the two patient groups. However, the range of values found in the RA membranes appeared to be slightly higher in comparison to previously reported values for RA synovial fluid, peripheral blood and eluted synovial membrane T cells. Analysis of the relative proportions of the V delta 1+ and V delta 2+ subsets revealed a significant dominance of V delta 1+ cells in RA membranes and approximately equal numbers of the two populations in the JRA patients. As the majority of peripheral blood TCR gamma/delta+ cells use the V delta 2 segment this suggests a preferential homing or expansion of the V delta 1+ cells in both RA and JRA synovium. The overall distribution pattern of the TCR gamma/delta+ and V delta 1+ and V delta 2+ cells was also recorded. These cells mostly accumulated in the lymphoid-like tissues and in the perivascular area in the tissues of both RA and JRA patients. Occasionally, augmented numbers of these cells were found in the subsynovial layer or in the loose connective tissue. In the majority of cases, only a few TCR gamma/delta+ cells were located in the synovial layer. The function and the possible pathogenetic importance of these TCR gamma/delta+ cells have not so far been determined.

Adolescent↗

Updating one's knowledge about the current status of vehicles in a freight system simulation.

The use of simulations of real-world settings can provide data relevant to ergonomics problems in a wide range of similar settings. This paper reports on a simulation of a freight service operation. It examines the effect of manipulating the type and format of information representation on the ability to update knowledge about the status of three vehicles. In addition, the effects of display type and the detection of violations of pre-learned rules on the ability to update are examined. The display format proved not to be a critical factor but the requirement to detect rule violations of a specific vehicle resulted in better memory-updating performance for that vehicle. The results are discussed in terms of a human memory mechanism, which is analogous to a computer operating system, involved in updating memory and detecting violations. Finally, the value of using this tool to examine complex cognitive processes relevant to the workplace is discussed.

Journal Article↗

Immunosuppression by seminal plasma from fertile and infertile men: inhibition of natural killer cell function correlates with seminal PG concentration.

Human seminal plasma has uniquely high concentrations of PGE and 19-hydroxy PGE but the function of these PGs has not been elucidated. PGs of the E series have been shown to be paracrine and autocrine regulators of the function of immune cells and high levels of PGE have been shown consistently to suppress function in such cells. Human seminal plasma has a potent immunosuppressive effect and evidence is accumulating that this is largely due to PG components. In this study the effects of human seminal plasma on the killing activity of natural killer (NK) cells as judged by 51Cr release from K562 cells have been studied in groups of fertile and infertile men. Although there was no significant difference in the PGE, 19-hydroxy PGE or the NK cell inhibitory activity in the two groups, the inhibition of NK cell activity was closely correlated with the PGE and the 19-OH PGE content of the seminal plasma in the fertile group. This finding is further evidence that the major contribution to the immunosuppressive properties of human semen is provide by the high concentration of PGs of the E series in this fluid.

Alprostadil↗

Immune responses to 18.6 and 30-kDa mycobacterial antigens in rheumatoid patients, and V beta usage by specific synovial T-cell lines and fresh T cells.

We have investigated both the humoral and the cellular immune responses of patients with juvenile rheumatoid arthritis (JRA) and rheumatoid arthritis (RA) to mycobacterial antigens. The JRA group was not Bacillus Calmette Guerin (BCG) vaccinated whilst the majority of the RA group was. As determined by immunoblotting, 79% of sera from patients with JRA reacted mainly with a 18.6-kDa protein (P18.6), whilst 70% of sera from patients with RA reacted mainly with a 30-kDa protein (P30) of BCG, M. tuberculosis and M. kansasii. In contrast, only a moderate proportion of the control sera (25% of adult and 20% of children) showed reactivity to P30, and none of the samples had significant reactivity with the P18.6 antigen. Furthermore, T-cell proliferation to the P18.6 and P30 antigens was detected in the majority of JRA and RA patients, and was nearly always higher in synovial fluid (SF) than in the peripheral blood (PB). We also investigated the usage of V beta family genes in P18.6 and P30 antigen-specific T-cell lines established from the SF of one patient with active RA. We showed that V beta 2, -4, -5, -6, -7, -14, -17, -18 and V beta 19 were over-represented compared with other known V beta families. We also noted that the proportion of V beta 14 was higher in freshly isolated SF mononuclear cells compared with the blood in this patient and in 2 out of 4 other RA patients examined. Other V beta families such as V beta 6, V beta 8, V beta 16, V beta 18 and V beta 19 were also over-represented in the SF compared with the blood in some patients. Taken together our results provide more information concerning the role of mycobacterial antigens in RA and suggest that there may be an in vivo clonal expansion of T lymphocytes in the synovium.

Adult↗

Immunosuppression by seminal plasma and its possible biological significance.

The data support the role of seminal plasma facilitating the transmission of virus and establishment of infection when all depositions of semen occur, but systemic absorption would also be possible by vaginal intercourse if lesions or abrasions caused for example by other s.t.d's, were present. The severity and rapid increase in the population of certain sexually transmitted agents make it imperative that epidemiological studies are initiated to study any correlation with changes in sexual behaviour and contraceptive practices. Finally, further isolation and characterization of seminal plasma components should lead to a clear understanding of their action as both regulatory molecules and in their possible contribution to disease.

Humans↗

Immunosuppression by seminal prostaglandins.

In this paper we report studies undertaken to determine the contribution of seminal prostaglandins to some of the known immunosuppressive properties of human seminal plasma. Initial studies revealed that fractions of seminal plasma enriched in E series prostaglandins, obtained by reverse phase chromatography, had a pronounced inhibitory effect on the PHA-induced proliferation of peripheral blood lymphocytes and on the NK-cell-mediated lysis of K562 target cells. Additional investigations revealed that similar inhibitory effects could be achieved with purified PGE2 (10(-6) to 10(-9) M) and 19-OH PGE1 (10(-6) to 10(-7) M), both of which are present in uniquely high concentrations in human seminal plasma. In contrast, 19-OH PGF1 which is found in lower concentrations in semen was slightly stimulatory in proliferative assays and had no effect on NK-cell-mediated cytotoxicity. Removal of the seminal prostaglandins by absorption chromatography resulted in a dramatic decrease in immune suppressive activity. Further studies with fractions obtained by ion-exchange HPLC of desalted seminal plasma indicated that prostaglandins complexed with seminal proteins, and these too were immunosuppressive. The possible relevance of these results to sexually transmitted disease is discussed.

Cytotoxicity, Immunologic↗

The psychology of briefing. A review and seven recommendations for improving performance.

In many operational settings, briefings take place at the beginning of a work period. Often, such briefings are made without much forethought and training. This article outlines some of the problems that are likely to be encountered in such situations and provides seven recommendations that should improve the memorability and comprehensibility of briefing sessions. It is recommended that briefings should begin with an outline of the critical points, be devoid of unnecessary detail and be confined to not more than six topics. Guidelines are provided for the use of pictures and graphs and combining these with verbal descriptions. The value of handouts and the use of summaries and prompts at the end of the briefing session are also considered.

Journal Article↗

Human seminal plasma suppresses lymphocyte responses in vitro in serum-free medium.

The in vitro immunosuppressive properties of human seminal plasma have been re-investigated in serum-free medium in view of recent suggestions that the previously observed effects might be dependent on the presence of exogenous serum co-factors present in the culture media. The present studies reveal that low concentrations of seminal plasma can inhibit the ability of peripheral blood leukocytes to lyse K562 target cells in the absence of fetal calf or new-born calf serum. These inhibitory effects could be achieved by pre-incubating the effector cells in seminal plasma at 37 degrees C prior to use in the natural killer cell assay or by incorporating it into the assay system. Additional studies revealed that human seminal plasma could also inhibit the proliferative response of peripheral blood lymphocytes to phytohaemagglutinin in serum-free HB103 medium. These effects were most marked and consistent if the seminal plasma was present throughout the period of culture. Overall, these studies indicate that the previously reported suppressive effects of human seminal plasma in these systems cannot be entirely attributable to cytotoxic factors generated by exogenous serum components.

Culture Media↗

Studies on the immunosuppressive effect of seminal plasma.

In vitro suppression of immune responses by seminal plasma is well documented, but the mechanism by which it exerts its effects remains to be established. Our studies on T-lymphocyte proliferation and natural killer cell target-cell lysis reveal that seminal plasma mediated suppression is dose-dependent and temperature-dependent, and that cells which have been activated are less susceptible to suppression. In the case of mitogen-induced T-cell responses this results in a decrease in the expression of the Interleukin-2 receptor whose generation is essential to T-cell proliferation. These studies provide further evidence about suppression of the immune response by seminal plasma. This may be a contributory factor in the aetiology of AIDS, other sexually transmitted diseases, infertility and malignancies of the urogenital tract including carcinoma of the cervix.

Cell Division↗

The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells.

The female reproductive tract is immunologically unique in its requirement for tolerance to allogeneic sperm and, in the upper tract, to the conceptus. However, it must also be appropriately protected from, and respond to, a diverse array of sexually transmitted pathogens. Some of these infections can be lethal (e.g. Human Immunodeficiency Virus (HIV), Human Papilloma Virus (HPV)), and others (e.g. Chlamydia trachomatis and Neisseria gonorrhoeae) can have potentially devastating reproductive sequelae. Interactions between a host and a pathogen are complex, diverse and regulated, and are a function of the individual pathogen, and host immunity. Although there is undoubtedly commonality in the mucosal immune response, there is also evidence of a degree of site-specificity in immune mechanisms, dependent upon the function and anatomical location of an organ. In this article, we review the evidence on the pivotal role of epithelial cells in the innate and early immune response to pathogen challenge in female genital tract tissues, and examine the evidence that the 'sterile' upper and the 'non-sterile' lower female genital tract may maintain a different immunological surveillance milieu, and may also respond differentially to pathogen challenge. We also review the unique characteristics, and subsequent ramifications of the acute cervical immune response to C. trachomatis, and discuss how natural antimicrobial mediators of immunity may be utilized to decrease the spread of sexually transmitted infections.

Animals↗