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Biomedical subjects

M Londei

Publications and source records attributed to M Londei.

At least 109 records · Page 6Linked to original sources
PubMed1987

Human T cells from autoimmune and normal individuals can produce tumor necrosis factor.

T cell clones derived from patients with autoimmune diseases were found to be capable of producing tumor necrosis factor (TNF). This was demonstrated by stimulating the clones, in the absence of accessory cells, with antibodies against the Ti/T3 complex and with recombinant interleukin 2 (IL2). Analysis of RNA extracted from these clones showed that TNF mRNA was more abundant than lymphotoxin (LT) mRNA. We also found that TNF protein in the supernatants of these clones was generally more abundant than LT as assessed by using the murine L929 cell assay. TNF production was not limited to T cells from autoimmune individuals, since the T cell tumor HUT78 and T cells purified from the peripheral blood of healthy individuals also made TNF. Unlike the T cell clones, HUT78 produced greater amounts of LT mRNA than TNF mRNA. Induction of TNF mRNA in T cells from healthy individuals displayed a two-signal requirement (phorbol myristate 13-acetate and phytohemagglutinin or OKT3 and phorbol myristate 13-acetate), similar to that described for the induction of the T cell lymphokines IL 2 and interferon-gamma (IFN-gamma). Additionally we found that IL2 alone was sufficient to induce TNF in these cells when they had been precultured with phytohemagglutinin for 7 days to express IL 2 receptors. The cloned T cells we have characterized also produce IFN-gamma which was detected in the supernatants of the clones using a radioimmunoassay. The evidence suggests that T cells can produce TNF and have the potential to deliver by themselves the dual and synergistic signals of TNF/LT and IFN-gamma to target cells, a process which may be of importance in the pathogenesis of human autoimmunity.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

New ideas in thyroid autoimmunity.

Endocrine epithelial cells do not normally express human leukocyte antigen (HLA) class II molecules, but do so in a variety of autoimmune diseases. This finding suggests the hypothesis that such inappropriate class II-positive expression may enable these cells to present autoantigens and thus contribute to autoimmune pathogenesis. Indeed, class II-positive thyrocytes can present both exogenous antigenic peptides and intrinsic autoantigens to the appropriate T cells. Class II expression by thyrocytes can be induced by interferon-gamma, and is positively and negatively regulated by thyroid-stimulating hormone and epidermal growth factor, respectively. Furthermore, heterogeneity of thyrocyte class II subregion expression appears to be related to the nature of the inducing stimulus. The complexity of regulatory signals is underlined by findings in type I diabetes: islet beta cells aberrantly express class II in this disease, but class II cannot be induced in normal beta cells by interferon-gamma.

Antigen-Presenting Cells↗
PubMed1986

HLA-D/DR expression on epithelial cells: the finger on the trigger?

The findings we have described here show a clear association between epithelial HLA-D/DR expression and autoimmunity. Furthermore, the ability of class II+ thyrocytes to present both exogenous antigens and autoantigens indicates an active role for these HLA-D/DR molecules in autoimmune pathogenesis. IFN-gamma is capable of inducing HLA-D/DR expression by thyroid epithelium, but a number of observations suggest the involvement of other inducers as well. Overall, we conclude that epithelial class II expression very probably plays a key role in the propagation and also in possibly the initiation of autoimmune attack. This is in accord with the proposal of a more general relationship between inappropriate or excessive class II expression and pathogenesis.

Antigen-Presenting Cells↗
PubMed1986

Gluten specific suppressor T cell dysfunction in coeliac disease.

A T lymphocyte direct migration inhibition factor test has been used to investigate the function of the specific suppressor T cell population controlling the immune response to gluten in coeliac disease. The test has been carried out in 21 adult coeliac patients, 22 Mantoux- healthy controls and eight Mantoux+ donors using gluten fraction III and purified protein derivative, as antigens. All coeliacs, but two, were Mantoux-. When gluten fraction III was used a significant migration inhibition was observed in coeliac patients compared to controls; such migration inhibition was abrogated by coculturing in a 1:1 ratio coeliac T cells with T cells from controls or Mantoux+ donors. On the contrary, the addition to coeliac T cells of T lymphocytes from other coeliacs did not abolish migration inhibition to gluten. Pretreatment of normal T cells with mitomycin C prevented their abrogating activity on migration inhibition of coeliac T lymphocytes. When purified protein derivative was used as antigen a significant migration inhibition was observed in Mantoux+ donors compared with healthy subjects and such migration inhibition was abolished by co-culturing T cells from Mantoux+ donors with those from Mantoux- controls and coeliac patients. Our results show that coeliac T cells, while retaining their ability to suppress the immune response to purified protein derivative, cannot suppress the immune response to gluten and are consistent with the hypothesis that a gluten specific suppressor T cell dysfunction, rather than a generalised T lymphocyte defect, may play a role in the pathogenesis of coeliac disease.

Adult↗
PubMed1986

Inappropriate major histocompatibility complex class II expression by thyroid follicular cells in thyroid autoimmune disease and by pancreatic beta cells in type I diabetes.

"Inappropriate" expression of class II major histocompatibility complex (MHC) molecules by target cells has been found in all organ-specific autoimmune diseases so far examined for the presence of this phenomenon. These glycoproteins may have a functional role as class II+ thyrocytes are able to present both small fragments of foreign antigens and autoantigens to helper T cells. Interferon gamma is a likely modulator of MHC class II expression in the thyroid but other signals like thyroid-stimulating hormone seem to influence its action. By contrast, it appears that lymphokines are not involved in inducing the inappropriate MHC class II expression observed in situ in the pancreatic beta cells of diabetics. These data suggest that regulation of MHC class II expression is different in thyroid follicular cells from pancreatic beta cells, and that similar differences may be found in other cell types involved in autoimmune disease, thus reinforcing the concept of heterogeneity in the pathogenesis of organ-specific autoimmune disorders.

Antigen-Presenting Cells↗
PubMed1985

Human T-cell clones from autoimmune thyroid glands: specific recognition of autologous thyroid cells.

The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatibility antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

Animals↗
PubMed1985

Specificity of leucocyte migration inhibition test in coeliac disease. A reassessment using different gluten subfractions.

Production of leucocyte migration inhibition factor by peripheral blood leucocytes in response to challenge with gluten fractions has been proposed as a reliable in vitro test for the diagnosis of coeliac disease. We have performed the leucocyte migration inhibition test with two different gluten fractions, GFIII and B2, in untreated and treated coeliac patients, patients with other intestinal diseases (abnormal controls) and healthy controls, and evaluated the sensitivity, specificity and positive and negative predictability of the test for the diagnosis of coeliac disease. Using GFIII as antigen leucocyte migration was significantly inhibited, compared to healthy controls, not only in treated and untreated coeliacs but also in abnormal controls. Using B2 gluten subfraction as antigen only treated coeliacs and abnormal controls differed significantly from healthy controls. The elevated number of abnormal controls showing migration inhibition consistently affected the diagnostic value of the test, which did not vary using B2 subfraction instead of GFIII as antigen. Our study confirms previous observations of gluten sensitization, as detected by leucocyte migration inhibition, in coeliac patients but strongly questions the claim that coeliac disease can be diagnosed on the basis of a positive leucocyte migration inhibition test without the need for intestinal biopsy.

Adolescent↗
PubMed1983

T-lymphocyte subsets in adult coeliac disease.

1. As a defect of suppressor function has been hypothesized in the pathogenesis of coeliac disease, we measured, by monoclonal antibodies, the inducer/suppressor T-cell ratio in adult coeliac disease. 2. No statistical difference was observed between coeliac patients and healthy controls, irrespective of treatment and HLA status. 3. These results do not show an imbalance in the inducer/suppressor T-cell ratio in coeliac disease.

Adult↗