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Biomedical subjects

M Londei

Publications and source records attributed to M Londei.

At least 91 records · Page 5Linked to original sources
PubMed1989

Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1989

Definition of a population of CD4-8- T cells that express the alpha beta T-cell receptor and respond to interleukins 2, 3, and 4.

Whereas most T cells express surface CD4 or CD8 molecules, a minority lacks both. CD4-8- cells usually express the gamma delta T-cell receptor, but here we describe a population of CD4-8- T cells from the peripheral blood that express the alpha beta heterodimer. These cells have different surface antigens than gamma delta+ T cells, expressing CD5 but lacking CD16, and differ in function from gamma delta+ T cells. CD4-8- alpha beta+ cells lack non-major histocompatibility complex-restricted cytolytic function but can be induced to lyse their target cells after activation of their T-cell receptors. A peculiar characteristic of these cells is their responsiveness to interleukin 3. Since these cells have not altered their phenotype or function over a 12-month period in culture, they appear to be mature T cells. The results indicate that normal human peripheral blood contains two subsets of CD4-8- T cells, expressing either gamma delta or alpha beta receptors, that differ in function, phenotype, and growth control.

Antigens, CD↗
PubMed1989

T cells and lymphokines.

T lymphocytes are one of the richest sources of protein mediators. Many of their effects, such as T cell help, growth stimulation, macrophage activation or suppression are caused by the release of these molecular mediators, which include the interleukins IL-2, IL-3, IL-4, IL-5, IL-6, interferons alpha and beta (IFN alpha and beta), tumour necrosis factor (TNF), lymphotoxin (LT), granulocyte macrophage colony stimulating factor (GM-CSF) and transforming growth factor beta (TGF beta). These molecules are only produced transiently after activation of the cells, and the CD4 (cluster differentiation antigen 4) cells are the richest sources of cytokines.

Animals↗
PubMed1989

Transforming growth factor beta regulates thyroid growth. Role in the pathogenesis of nontoxic goiter.

The production and growth regulatory activity of transforming growth factor beta were studied in human thyroid tissue. As estimated by its mRNA expression in fresh tissue samples, transforming growth factor beta was produced in normal and in diseased thyroid glands. Transforming growth factor beta mRNA was mainly produced by thyroid follicular cells and in lesser quantities by thyroid infiltrating mononuclear cells. The concentrations of transforming growth factor beta mRNA were lower in iodine-deficient nontoxic goiter than in Graves' disease and normal thyroid tissue. Transforming growth factor beta protein secretion by cultured thyroid follicular cells was also low in nontoxic goiter, but could be increased by addition of sodium iodide (10 microM) to the culture medium. Recombinant transforming growth factor beta did not affect basal tritiated thymidine incorporation in cultured thyroid follicular cells, but inhibited, at a concentration of 10 ng/ml, the growth stimulatory influence of insulin-like growth factor I, epidermal growth factor, transforming growth factor alpha, TSH, and partly that of normal human serum on cultured thyroid follicular cells. This inhibition was greater in Graves' disease than in nontoxic goiter. These results suggest that transforming growth factor beta may act as an autocrine growth inhibitor on thyroid follicular cells. Decreased transforming growth factor beta production and decreased responsiveness to transforming growth factor beta may be cofactors in the pathogenesis of iodine-deficient nontoxic goiter.

Adult↗
PubMed1989

Tumour necrosis factor synergises with gamma interferon on the induction of mRNA for DR alpha chain on thyrocytes from Graves' disease and non toxic goitre.

In both thyroid autoimmune diseases Graves' and Hashimoto's thyroiditis, the epithelial thyroid follicular cells (TFC) have been shown to express HLA class II molecules, and can restimulate autoreactive T cells cloned from the diseased tissue. This aberrant class II expression is important in the mechanism of perpetuation of the disease process, therefore we have compared the effect of interferon gamma (IFN gamma) and tumour necrosis factor (TNF alpha) on the HLA-DR alpha mRNA expression of thyroid follicular cells derived from Graves' disease (GD) and a non autoimmune disease, non toxic goitre (NTG). Our results indicate that TNF alpha synergises with IFN gamma in the induction of HLA class II mRNA. There was no consistent difference in DR alpha mRNA expression between the GD and NTG thyroid follicular cell preparations in response to induction by a combination of these lymphokines at various concentrations. Our data suggest that the differences in the level of expression of class II molecules observed in vivo in Graves' disease and non toxic goitre, which is much higher in the former, is probably due to local release of lymphokines by infiltrating T lymphocytes, although other factors may be involved.

Drug Synergism↗
PubMed1989

Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6.

Cytokine production was studied in thyroid tissue from patients with Graves' disease, Hashimoto's thyroiditis and non-toxic goitre. The expression of interferon gamma, tumour necrosis factor alpha and beta, interleukin-1 alpha and beta, interleukin-6 and platelet-derived growth factor A chain was assessed by slot-blot analysis of the respective mRNA in freshly isolated tissue samples. All seven cytokines were detected in patients of all groups. Although the respective mRNA levels were, in general, higher in thyroid autoimmune disorders, this appeared to relate to the degree of the lymphocytic infiltration of the thyroid gland at the time of surgery. Purified thyroid follicular cells expressed high levels of interleukin-1 alpha and interleukin-6 mRNA and when established in primary culture, purified thyroid follicular cells from Graves' disease as well as non-toxic goitre produced interleukin-1 alpha and interleukin-6 bioactivity spontaneously. In the case of interleukin-1 this could be further augmented by addition of lipopolysaccharide to the thyroid follicular cell cultures. These results demonstrate that the lymphocytic infiltrate found in autoimmune and non-autoimmune thyroid disorders is associated with cytokine production. Additionally we have shown that intrathyroidal cytokine production is not restricted to thyroid-infiltrating mononuclear cells, but may also involve thyroid follicular cells both in vivo and in vitro. The cytokines produced by thyroid follicular cells may have an important role in stimulating autoantigen specific T cells in vivo as both interleukin-1 and interleukin-6 facilitate T cell activation.

Adult↗
PubMed1988

Do CD4-positive cytotoxic T cells damage islet beta cells in type 1 diabetes?

The mechanism by which islet beta cells are destroyed in type 1 diabetes is still unknown. Because in diabetes the majority of T cells activated in vivo express CD4 and the islet beta cells selectively express the HLA class II antigens needed for recognition by CD4-positive T cells, the possibility that selective damage to islet beta cells may be caused by CD4-positive cytotoxic cells was investigated. Activated T cells were cloned from a newly diagnosed diabetic patient, and many CD4 cytotoxic clones were detected. The clone with the highest cytolytic capacity lysed HLA class II compatible islet cells which had been induced by interferon gamma and tumour necrosis factor to express class II antigens. The specificity of the lysis was demonstrated by use of histoincompatible islets, other histocompatible target cells, and blocking by anti-class-II monoclonal antibodies. The results show that a CD4-positive T cell clone can lyse HLA class II matched islet cells; this process may be important in the pathogenesis of type 1 diabetes.

Adult↗
PubMed1988

Campylobacter pylori in abattoir workers: is it a zoonosis?

Sera from 98 abattoir workers were tested for IgG to Campylobacter pylori, C jejuni, and klebsiella. Clerical workers had significantly lower C pylori and C jejuni IgG titres than any of the groups in direct contact with freshly cut animal parts. No difference was found for antibodies to klebsiella. 28 non-clerical workers with high-titre C pylori IgG consented to upper gastrointestinal endoscopy. C pylori associated gastritis was found in all 28, and four weeks of colloidal bismuth subcitrate (240 mg twice daily) was prescribed. On repeat testing at three months all showed a decrease in IgG titres to C pylori but not to C jejuni, whereas 18 untreated non-endoscoped workers showed no change. These findings raise the possibility that C pylori infection is a zoonosis.

Abattoirs↗
PubMed1988

T cells expressing gamma delta chain receptors in rheumatoid arthritis.

Whereas the majority of T cells use alpha and beta chains to form their T-cell receptor, a small minority of T cells, which do not express the CD4 or CD8 surface markers, use other chains termed gamma and delta to form their receptor. Flow cytometry was performed on cells isolated from the blood and synovial joints of patients with rheumatoid arthritis. Monoclonals which recognise the gamma and delta chains were used to compare the proportion of TCR gamma delta cells in these sites. Approximately half the patients had more TCR gamma delta in the joints than in their blood and one newly diagnosed patient had high numbers of TCR gamma delta cells in both blood and joints. In this preliminary study it is not possible to evaluate the role of these cells in the disease process, but it is of interest that in some RA patients there is an overabundance of both T cells that arise early in ontogeny (TCR gamma delta cells) and B cells that arise early in ontogeny, the CD5 B cell.

Antibodies, Monoclonal↗
PubMed1988

Efficient propagation and cloning of human T cells in the absence of antigen by means of OKT3, interleukin 2, and antigen-presenting cells.

The analysis of T lymphocytes infiltrating tissues afflicted by autoimmune diseases may provide major clues towards understanding the pathogenesis of such diseases. Currently the best approach to studying heterogeneous populations such as T lymphocytes involves long-term culture and cloning. In order to grow and clone T lymphocytes, regular restimulation with the specific antigen is essential, otherwise growth will stop and/or specificity may be lost. In autoimmune diseases the antigens involved in triggering the immunological reaction of T cells are usually unknown. Therefore an alternative way of stimulating T lymphocytes without loss of specificity is clearly needed. Here we describe the cloning and expansion of antigen-specific T cell clones from the blood of a healthy donor to sizeable numbers of cells (greater than 10(8)) by means of anti-CD3 monoclonal antibody and recombinant IL-2. The results obtained showed that this approach can be used to clone and 'expand' T lymphocytes that retain antigen specificity over a prolonged period, in this case over 10 weeks. This technique has been used to clone and expand T lymphocytes infiltrating the affected tissues in a variety of autoimmune disorders such as Hashimoto's thyroiditis, Graves' disease, and rheumatoid arthritis, and is an efficient method of propagating T cells, by mimicking the antigenic stimulus.

Antibodies, Monoclonal↗
PubMed1988

Pathogenetic relevance of HLA class II expressing thyroid follicular cells in nontoxic Goiter and in Graves' disease.

HLA class II expressing thyroid follicular cells are found not only in classical thyroid autoimmune diseases, such as Graves' disease, but also in presumably nonautoimmune thyroid disorders such as nontoxic goiter. In this study the immunostimulatory function of the HLA class II expressing thyroid follicular cells derived from patients with nontoxic goiter and with Graves' disease was compared by assessing their capacity to stimulate allogeneic and autologous peripheral blood mononuclear cells, as well as cultured intrathyriodal T lymphocytes. Proliferation of allogeneic peripheral blood mononuclear cells was stimulated by thyroid follicular cells from both nontoxic goiter and Graves' disease thyroids, thus demonstrating that thyroid follicular cells from both disorders are capable of presenting alloantigens. In contrast the proliferation of autologous peripheral blood mononuclear cells was more efficiently stimulated by thyroid follicular cells from Graves' disease than from nontoxic goiter. Cultured intrathyroidal T lymphocytes proliferated specifically in response to autologous HLA class II+ thyroid follicular cells in Graves' disease, but not in nontoxic goiter. The responses were dose dependent and HLA class II restricted. Thyroid autoantigen presentation by HLA class II expressing thyroid follicular cells thus only occurs in Graves' disease, suggesting that HLA class II expression on thyroid follicular cells is an essential feature, but by itself not sufficient for the induction of autoimmunity. Additional factors, the possible nature of which is discussed must also be involved.

Adult↗
PubMed1988

The majority of the activated T cells in the blood of insulin-dependent diabetes mellitus (IDDM) patients are CD4+.

Twenty-five recently diagnosed insulin-dependent diabetic patients were screened for the presence of activated T lymphocytes using the anti-IL-2 receptor monoclonal antibody; thirteen had elevated levels of activated T lymphocytes. The activated cells were mostly confined to the CD4 subset, with the CD4/CD8 ratio in IL-2 receptor expressing cells averaging 5 +/- 1 (s.d.) compared with 1.3 +/- 0.3 for all T cells. In recent onset insulin-dependent diabetes blood there was no lack of CD4 CD45R+ (suppressor/inducer) T cells. The activated IL-2 receptor, expressing cells belonged to both CD4 subsets, 'helper inducer' (CD44B4) and 'suppressor inducer', (CD42H4).

Adolescent↗
PubMed1988

Regulation of clonal growth by anti-T-cell receptor antibody-directed lysis.

CD4 and CD8 T-cell clones were generated using the Mx9 monoclonal antibody (mAb), which recognizes the V beta 8 T-cell receptor (TcR) gene family. The interaction of these clones with the Mx9 antibody was analysed and all were found to be specifically stimulated to proliferate by plastic-adherent Mx9. In the presence of Mx9 or its F(ab')2 fragment, CD8+ Mx9+ clones were capable of specifically lysing the CD4+ Mx9+ T-cell clones. No lysis was seen of Mx9- T cells, or in the absence of the antibody. Conversely CD4+ Mx9+ T cells did not have lytic function. These results indicate that cross-linking of T cells via their antigen-specific receptors may initiate a unidirectional killing. Unlike previously reported lytic systems involving anti-TcR antibodies (e.g. anti-CD3), these results suggest that this mechanism may have an important physiological role in immune regulation. Anti-idiotypic antibodies have been shown to recognize T-cell receptors. These may exert profound immunosuppressive effects by inducing the lysis of the helper cells or B cells.

Cell Division↗
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↗