PubMed Health⌕ Search

Biomedical subjects

A Boylston

Publications and source records attributed to A Boylston.

At least 19 recordsLinked to original sources
PubMed2002

T cell receptor usage in patients with non-progressing HIV infection.

It is still unclear why some patients with HIV progress more slowly than others to developing full blown AIDS. In this study using flow cytometry we have investigated the TCRBV repertoire of peripheral blood T lymphocytes in 17 long-term non-progressing HIV patients (LTNP) to determine if there is a biased usage of T cell receptor V gene products. Patients were identified from hospital records and entered into the study. Three colour flow cytometry was used to determine the expression of the TCRBV3S5, BV5S1, BV5S2, BV5S3, BV6S1, BV7S1, BV9, BV11, BV12, BV13, BV14, BV16, BV17, BV18, BV20, BV21S3, BV22, and BV23 by CD8 and CD4 positive cells isolated from the peripheral blood of patients and controls. Increases in the absolute numbers of CD8+ T cells expressing TCRBV2 and 8 were observed in the HIV-LTNP population (P < 0.05 in both cases). No differences were seen in numbers of CD8+ T cells expressing other TCRBV or in any TCRBV within the CD4+ T cell popu-lation. At follow up (1-2 years later), those patients in which CD4 levels were below 500 x 106/l were those initially found to have lower levels of TCRBV8 +ve CD8 cells. A significant increase in the absolute numbers of T cells coexpressing the gamma delta (gammadelta) T cell receptor and CD8 were also seen in the HIV-LTNP patients compared with controls (P = 0.002). The increase in CD8+ T cells in the HIV-LTNP patients may be interpreted as either an antigen specific, or group of antigen specific responses to viral antigen, or less likely a viral superantigen. A low level of TCRBV8, CD8+ T cells might be predictive of a more rapid disease progression and might indicate a protective role for this population in HIV infected patients. The increase in gammadeltaT cells bearing the CD8 coreceptor suggests a role for this cell type in the response to HIV infection.

Adult↗
PubMed1998

Rib lesions and tuberculosis: the palaeopathological evidence.

SETTING: Tuberculosis diagnosis in past populations relies on lesions in the spine and major weight bearing joints of the body. Bone formation on visceral surfaces of ribs has also been suggested to be the result of chronic pulmonary disease. OBJECTIVE: To test whether these lesions are the result of pulmonary infection (most likely tuberculosis), by reviewing past work, and to discuss whether these lesions could be considered another diagnostic criterion for pulmonary tuberculosis. DESIGN: A review of the literature on new bone formation on ribs, and consideration of further evidence from archaeological skeletal material from the UK. RESULTS: Results from modern studies suggest that bone formation on ribs is often the result of pulmonary tuberculosis, that lesions are relatively common in archaeological skeletal material, and that some skeletons have rib lesions plus pathognomonic changes of tuberculosis. CONCLUSION: Evidence suggests that new bone formation on visceral surfaces of ribs should be considered a possible indicator of tuberculosis. If accepted, historical evidence, when correlated with rib data, produces closer approximations to the frequency of the disease in the past. This study indicates the importance of palaeopathology in identifying sometimes subtle lesions that may not be noted by clinicians because of their non-visibility on radiographs.

Humans↗
PubMed1997

Streptococcus pyogenes type 5 M protein is an antigen, not a superantigen, for human T cells.

M proteins are coiled-coil dimers expressed on group A streptococcal cell surfaces. They have an important role in host antistreptococcal immunity and in poststreptococcal autoimmune sequelae. Controversy has arisen regarding whether type 5 M proteins are superantigenic for human T cells. To investigate this, we have produced and tested M5 in the form of two novel recombinant proteins. We found no evidence of superantigenicity using either recombinant whole M5 protein (rM5) or recombinant pep M5 protein (rpepM5) to activate peripheral blood mononuclear cells (PBMC) from healthy adult volunteers. Short-term, rM5-specific T-cell lines from different subjects were uniformly self-APC restricted and showed no consistent pattern of TCR V beta usage. A synthetic peptide of M5 residues 217-237 was found to contain epitope(s) recognized by some rM5-specific human T cells. PBMC responses to rM5 and rpepM5 in 3- and 7-day proliferation assays were characteristic of antigenic rather than superantigenic stimulation. We conclude that type 5 M protein activates human T cells as a conventional antigen.

Adult↗
PubMed1996

Brief communication: when Adam delved ... an activity-related lesion in three human skeletal populations.

A rare, activity-related lesion, the clay-shoveller's fracture, was identified during osteological analysis in three human populations dating from the Roman to the later Medieval period in England, circa fourth to 14th centuries A.D. The prevalence of this fracture in these populations suggests an osteological indicator for several possible manual activities, but also one that may be the result of a long-standing human subsistence adaptation requiring digging in the soil. Since males as opposed to females appear to be preferentially affected, the occurrence of such injuries has the potential to provide an insight into the sexual division of labor in earlier human populations.

Adult↗
PubMed1995

Influence of laparoscopic and conventional cholecystectomy upon cell-mediated immunity.

Surgery, trauma and anaesthesia induce a state of transient immunosuppression. Laparoscopic cholecystectomy has several well documented clinical advantages over traditional cholecystectomy and provokes a lower acute phase response, thought to be a result of the smaller wound size. The influence of laparoscopic cholecystectomy (21 patients) and conventional open cholecystectomy (13 patients) upon components of the cell-mediated immune system was investigated. Cell-mediated immunity was studied by in vitro assays of T lymphocyte proliferation to different mitogens, and by natural killer cell cytotoxicity using a standard 51Cr release assay. Blood samples were taken before and 24 h after the start of the operation. In the sample taken after operation there was significant depression of T lymphocyte proliferation to phytohaemagglutinin (stimulation index 149.4 versus 33.3, P < 0.002), staphylococcal enterotoxin B (85.2 versus 52.6, P = 0.01) and toxic shock syndrome toxin (48.4 versus 14.8, P = 0.08) in the group of patients who underwent open surgery, but not in the group treated by laparoscopic surgery. There was a small but statistically insignificant decrease of natural killer cell cytotoxicity in both groups of patients. These findings suggest that laparoscopic cholecystectomy causes less depression of cell-mediated immunity than open cholecystectomy.

Adult↗
PubMed1995

The immunomodulatory effect of levamisole is influenced by postoperative changes and type of lymphocyte stimulant.

The results of both laboratory and clinical research into the immunomodulatory activity of levamisole have shown a considerable degree of inconsistency and sometimes contradiction. This is probably a reflection of the lack of understanding of the mechanism(s) of action of levamisole and it is therefore necessary to base conclusions about its immunomodulatory efficacy in the treatment of disease on experimental assays that take into consideration the in vivo conditions. This investigation was designed to compare the immunomodulatory activity of levamisole under clinically achievable and non-achievable conditions as judged by changes in the perioperative proliferative response of lymphocytes from 30 patients with colorectal cancer. The results obtained showed that proliferation in antigen (purified protein derivative, PPD)-stimulated, but not phytohaemagglutinin(PHA)- or staphylococcal-enterotoxin-B(SEB)-stimulated, lymphocyte cultures was consistently and significantly augmented by levamisole in concentrations of 25 ng-25 micrograms/ml. High concentrations of levamisole (25 micrograms/ml and 100 micrograms/ml) were inhibitory to PHA- and SEB-stimulated, but not PPD-stimulated, lymphocyte cultures, especially in the postoperative period. Of particular interest was the observation that, although levamisole temporarily lost its stimulatory activity in the postoperative period (third postoperative day), it did enhance antigen-stimulated lymphocytes at the time of the nadir of the postoperative suppression of lymphocyte proliferation (first postoperative day). Clinically achievable concentrations of levamisole are therefore effective both before and after operation in enhancing the response of lymphocytes to antigens.

Adjuvants, Immunologic↗
PubMed1994

Selective expression of V beta families by T cells in the blood and salivary gland infiltrate of patients with primary Sjögren's syndrome.

OBJECTIVE: The T cell infiltration of the salivary gland of patients with Sjögren's syndrome (SS) has been implicated in the pathogenic process of the disease. We examined the representation of V beta subsets in the blood and salivary tissue of patients with SS. METHODS: Circulating T cells from 12 patients and paired samples of blood and labial salivary glands obtained from 8 patients were studied. A panel of monoclonal antibodies directed against the variable region of the T cell receptor was used to enumerate the cells expressing V beta families in the peripheral blood by flow cytometry, and in tissue sections by immunofluorescence. RESULTS: We found an increase of cells bearing V beta 2 family gene products in the circulation, and an increase in both V beta 2 and V beta 8 in the salivary gland infiltrate of patients with SS. No significant difference was noted between the 5 DR3+ patients and 7 DR3- patients studied with regard to the V beta families seen. CONCLUSION: Our data are consistent with a role for specific T cell families in the pathogenesis of SS.

Adult↗
PubMed1989

V beta-specific stimulation of human T cells by staphylococcal toxins.

The staphylococcal toxins are responsible for a number of diseases in man and other animals. Many of them have also long been known to be powerful T cell stimulants. They do not, however, stimulate all T cells. On the contrary, each toxin reacts with human T cells bearing particular V beta sequences as part of their receptors for major histocompatibility complex protein-associated antigen. The specificity of these toxins for V beta s puts them in the recently described class of superantigens and may account for the differential sensitivity of different individuals to the toxic effects of these proteins.

Antibodies↗
PubMed1988

Massive synchronous B-cell necrosis causing type 1 (insulin-dependent) diabetes--a unique histopathological case report.

A 22-year-old Chinese male died in hyperglycaemic coma following a 36-h illness. The only significant pathological findings were in the pancreas where there was a heavy diffuse infiltrate of lymphocytes admixed with numerous eosinophils, macrophages and polymorphs. There appeared to have been massive, recent, synchronous necrosis of insulin-secreting B cells with no destruction of any other pancreatic parenchymal cells. The biochemical findings of severe hyperglycaemia, insulinopoenia, but a normal glycosylated HbA1 were compatible with an acute onset to the patient's diabetes. These features contrast with the very much slower destruction of B cells associated with insulitis seen in "classical" Type 1 (insulin-dependent) diabetes.

Acute-Phase Reaction↗
PubMed1988

Lysis of CD3 hybridoma targets by cloned human CD4 lymphocytes.

UCHT1, a CD3-producing hybridoma, is lysed by cloned human T cells of both CD4 and CD8 phenotypes. The lysis is specific for the CD3 receptor and is mediated by 90% or more of all T cells from blood, without evidence for a subset of CD4 T cells incapable of cytotoxicity. CD4 clones characterized as 'helper' cells by in vitro help for specific antibody production by B cells also lysed CD3 targets. Varicella zoster virus (VZV) super-infected B lymphoblasts were lysed by three of six VZV-specific T-cell clones and 1 Cl-specific T-cell clones lysed 1 Cl hybridoma targets. Resting B cells (from tonsil) coated with CD3 antibody were lysed by CD4 clones. The data suggest that the majority of clonable CD4+ T cells lyse target cells recognized via CD3 or through the antigen receptor.

Antigens, Viral↗
PubMed1988

Heterogeneity of T cell receptor idiotypes in rheumatoid arthritis.

The nature of the T cell response in the rheumatoid synovium was investigated by using monoclonals MX9 and 42/1C1, which recognize the V beta 8 and V beta 5 T cell receptor gene families respectively. The blood and synovial T cells of ten patients with rheumatoid arthritis were compared. The majority (8/10) had different numbers of V beta 5 and V beta 8 cells in the joints from those in the blood, indicating that the T cells in the joints were not a sample of those in the blood. In three patients both V beta 5 and V beta 8 cells in the joint were augmented in number, suggesting that the T cells selectively retained in the joint were not members of a single clone, but derived from many clones. Some patients had increased levels of V beta 5 or V beta 8 alone in the joint indicating that heterogeneity existed between patients. These results are not consistent with the preferential or dominant use of a single V beta gene family in the T cells involved in the rheumatoid arthritic joints.

Arthritis, Rheumatoid↗
PubMed1987

The role of the T cell receptor, CD8, and LFA-1 in different stages of the cytolytic reaction mediated by alloreactive T lymphocyte clones.

The cytotoxic reaction mediated by cytotoxic T lymphocytes (CTL) consists of three phases: first, the CTL binds to the target cell; next, the CTL is triggered to lyse the target cell; and in the third phase, the CTL detaches from the target cell which is lysed in the absence of the CTL. Recently, we obtained evidence that human alloreactive CTL clones initially adhere to target cells without the involvement of the interaction between the T cell receptor (Tcr) and its specific target antigen. In the present study, we investigated the effect of monoclonal antibodies specific for the Tcr on the cytotoxic reaction of three CD8+ HLA-A2-specific CTL clones, using a single cell assay in which the binding event can be distinguished from the post-binding (lytic) phase of the cytolytic reaction. It was found that monoclonal antibodies directed at a variable part of the Tcr do not affect the binding phase but strongly block the lytic phase of the cytotoxic reaction. An anti-constant region Tcr antibody and an anti-CD3 reagent had a similar effect on the two phases of the reaction as the anti-variable part Tcr antibodies. In contrast, antibodies specific for LFA-1 strongly blocked the adhesion phase but did not affect the lytic phase. Antibodies specific for CD-8 had intermediate effects. They could block both the adhesion as well as the lytic phase. The effect of anti-CD8 appeared to be dependent on the CTL clone tested. One clone was found to be inhibited in the adhesion phase, but not in the lytic phase, whereas anti-CD8 hardly blocked the adhesion phase of two other CTL clones, but affected the lytic step of those clones. Our data indicate that LFA-1 is a major adhesion molecule in the CTL reaction, whereas the Tcr/CD3 complex is implicated in a phase after the initial formation of conjugates. CD8 is associated with both steps in the cytolytic reaction. In addition to its minor role in the adhesion phase, our data suggest strongly that CD-8 is involved in the triggering phase of the cytolytic reaction.

Antibodies, Monoclonal↗
PubMed1987

The T-cell receptor gamma chain-CD3 complex: implication in the cytotoxic activity of a CD3+ CD4- CD8- human natural killer clone.

A subset of human T cells has recently been described. These cells express the CD3 complex but they do not carry the classical T-cell receptor (TCR)-alpha/-beta heterodimer on their surface (WT31- CD3+). Instead, they express a TCR-gamma chain associated with another type of polypeptide termed TCR-delta. We report here that a T-cell clone with natural killer (NK)-like activity, WM-14, had a disulfide bridged TCR-gamma homodimer associated with CD3 on its surface. The TCR-gamma chains of WM-14 cells were present in three different glycosylation forms of 43, 40, and 38 kDa, but they appeared to contain the same polypeptide backbone. Since cytotoxicity by WM-14 could be inhibited by anti-CD3 antibodies, we concluded that the TCR-gamma-CD3 complex was involved in the NK-like unrestricted killer activity. Although normal CD3-gamma, CD3-delta, and CD3-epsilon chains were present in this clone, the association with the TCR-gamma homodimer may be the cause of a complete processing of the N-linked oligosaccharides attached to the CD3-delta chain.

Antibodies, Monoclonal↗
PubMed1987

Cytomegalovirus colitis and oesophageal ulceration in the context of AIDS: clinical manifestations and preliminary report of treatment with Foscarnet (phosphonoformate).

Three patients with biopsy diagnosed invasive cytomegalovirus infection of the colon have been seen in the context of the acquired immune deficiency syndrome (AIDS). Cytomegalovirus colitis presented with fever, abdominal distention, bloody diarrhoea and weight loss. Plain abdominal radiographs showed generalised large bowel dilatation in one patient. Cytomegalovirus infection was shown histologically, but the virus could not be cultured from the stool; no other gastrointestinal pathogens could be demonstrated. The patients were treated with a 14 day continuous infusion of Foscarnet 0.08 mg/kg/min (phosphonoformate, Astra Pharmaceuticals). One patient showed a partial response to therapy, but the cytomegalovirus colitis relapsed; the second patient had a symptomatic response only and the third patient died of non-cytomegalovirus opportunist infection while on treatment. Two other patients with biopsy proven cytomegalovirus ulceration of the oesophagus were seen, presenting with dysphagia, fever and weight loss. Invasive infection of the gastrointestinal tract with cytomegalovirus is now a major clinical problem in AIDS. Treatment with Foscarnet may be initially effective, but does not eliminate cytomegalovirus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Human fetal lymphocytes require T cell growth factors for cytotoxic responses.

Lymphocytes isolated from the blood of 17 human fetuses, varying in gestational age between 16 and 26 weeks, were tested for their capacity to generate specific cytotoxic cells after mixed lymphocyte culture (MLC) with allogeneic cells in the presence or absence of exogenous T cell growth factor (TCGF). Blood cells from seven fetuses, distributed throughout the age range, failed to generate cytotoxic cells even when TCGF was added in MLC, whereas six others gave positive responses but only when exogenous TCGF was present during the sensitisation phase. The maturation induced in the latter was not caused solely by a direct, non-specific effect of the TCGF, for control responder cells incubated with TCGF in the absence of allogeneic stimulator cells always responded less strongly or not at all. Fetal blood lymphocytes from the remaining four fetuses gave significant cytotoxic responses that were not augmented by TCGF. It is concluded that there can be a clear dichotomy between proliferative and cytotoxic responses to alloantigens and that the inability of human fetal blood lymphocytes to mount cytotoxic responses at this stage of development might be due to deficiencies in helper cells, cytotoxic precursors or both. For three fetuses it was possible to study, additionally, cytotoxic responses of spleen, liver and thymus with and without TCGF. None of them made specific responses even when TCGF was added, though cells from two spleens and one thymus responded directly to TCGF. To ascertain whether the absence of cytotoxic responses might have been caused by a failure of blood, spleen, thymus or liver cells to proliferate, their mixed lymphocyte reactivity, as detected by the uptake of 3H-thymidine, was studied without exogenous TCGF. Whereas thymus cells from only one of five fetuses responded, cells from all other tissues (including blood) responded consistently.

Adult↗
PubMed1986

T cell clones which share T cell receptor epitopes differ in phenotype, function and specificity.

Recently, we described a monoclonal antibody (3D6) that reacts with the T cell receptor (Ti) of the T leukemic cell line HPB-ALL and that cross-reacts with 2-10% of the T cells of normal healthy individuals. In this study we report the establishment of T cell clones that are 3D6+ but that differ in function and phenotype. These clones were established according to two different protocols: T cells of donor HY (10% 3D6+) were stimulated with the Epstein-Barr virus-transformed cell line JY. The proliferating 3D6+ T cells were enriched using a rosetting technique and cloned. T cells of donor HY were stimulated with the 3D6 antibody and subsequently expanded in recombinant interleukin 2-containing medium. This yielded 70% 3D6+ T cells which after activation with either Daudi cells or with TT in the presence of autologous non-T cells, followed by cloning, resulted in antigen-specific 3D6+ T cell clones. The 3D6+ T cell clones were also tested on their reactivity with 4 other monoclonal antibodies (1C1, 1C2, 2D4, 65) specific for the Ti of HPB-ALL. The antibodies 1C1 and 1C2 reacted with all 3D6+ T cell clones and recognize probably the same epitope as 3D6. The antibodies 2D4 and 65 reacted with two mutually exclusive subsets of T cell clones. All the anti-Ti antibodies reacted with functional epitopes, since they were able to block the function of the T cell clones. The specificity of the clones was investigated by blocking studies using monoclonal antibodies specific for different major histocompatibility complex antigens. No correlation was found between the expression of the different Ti epitopes and the specificity, the CD4/CD8 phenotype or function of the clones.

Antibodies, Monoclonal↗
PubMed1986

A family of T-cell receptor molecules expressed on T-cell clones with different specificities for allomajor histocompatibility antigens.

A monoclonal antibody, 3D6, identifies a public idiotope or allotope on the human T-cell receptor for antigen, since it not only reacts with the tumor line HPB-ALL, against which it has been raised, but also with 3-13% of peripheral blood T lymphocytes of normal donors. 3D6+ cells have been isolated from an allogeneic mixed lymphocyte culture and cloned by limiting dilution. In this way, allospecific clones were obtained both of the T4+T8- and the T4-T8+ phenotype, which included proliferative as well as cytotoxic cells. Within a panel of 20 cytotoxic clones, different specificities for both class I and class II MHC antigens were found. The clones were tested for their reactivities with four additional anti-T-cell receptor antibodies raised against HPB-ALL. Two of these, 1C1 and 1C2, reacted with all 3D6+ clones. By means of two other antibodies, 2D4 and 65, the 3D6+ receptor family could be divided into four structurally distinct subfamilies. Biochemical analysis suggested that the 1C1, 1C2, 2D4, and 3D6 antibodies define epitopes on the beta chain of the receptor. Isoelectric focusing of receptor molecules isolated from cytotoxic clones with different specificites indicated that there are extensive structural differences in both alpha and beta chains of the receptors. No correlation could be found between the antigenic specificity of a clone and the structure of its receptor in this analysis. It is postulated that the 1C1, 1C2, and 3D6 epitopes may be encoded by a particular germline V beta segment, in analogy with similar, previously described findings in both the human and the murine system.

Antibodies, Monoclonal↗