Rheumatoid Arthritis: Lydyard PM

Youinou P, Lydyard PM. · No affiliation provided · Lupus. · Pubmed #11530992 No free full text.

This publication has no abstract.

Dean GS, Anand A, Blofeld A, Isenberg DA, Lydyard PM. · Department of Immunology and Molecular Pathology, Royal Free and University College School of Medicine, London, UK. · Lupus. · Pubmed #12220104 No free full text.

Abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease that may affect every organ or system in the body. We have shown previously that the TCR alphabeta+ subpopulation of CD3+ CD4- CD8-, DN T cells is expanded in patients with SLE and that double negative T cells express increased levels of activation markers compared both with healthy people and with patients with rheumatoid arthritis, (RA) as autoimmune controls. The aim of this study was to characterize these cells in terms of their ability to produce IL4, a Th2 cytokine, both spontaneously and after mitogen stimulation. It was found that a higher percentage of TCR alphabeta+ double negative T cells from patients with SLE contained IL4 constitutively than did the same population of cells from healthy people or from those with RA. After mitogen stimulation, there was no significant difference in the amount of IL4 produced by each of the three groups. Further study of patients producing high levels of IL4 (about one third of the patients) indicated that they had a lower percentage of alphabeta+ T cells in the double negative compartment than did patients with fewer IL4 containing cells.

Anand A, Dean GS, Quereshi K, Isenberg DA, Lydyard PM. · Department of Immunology and Molecular Pathology, Royal Free and University College School of Medicine, London, UK. · Lupus. · Pubmed #12220103 No free full text.

Abstract: Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and the production of autoantibodies, some of which (antibodies to dsDNA) are thought to be pathogenic. T helper cells drive the production of autoantibodies and the aim of this study is to characterize phenotypically a subpopulation of T cells (the CD3+ CD4- CD8-, double negative (DN) T cells) previously identified as helping to enhance anti-DNA antibodies in patients with SLE. Data were obtained using FACS staining of DN T cells that had been purified from PBMCs by magnetic bead separation. The percentage of TCR alphabeta+ DN T cells was found to be significantly higher in patients with SLE as compared with controls (P = 0.02), although there was no significant increase in total percentage of DN T cells, which includes TCR gammadelta+ cells. Activation markers HLA-DR and CD69, the costimulatory molecule CD28 and CTLA-4 were all expressed on the surface of a higher percentage of DN T cells in patients with SLE than in patients with rheumatoid arthritis (RA) or healthy controls (HC). More DN T cells from patients with SLE were of CD45RA phenotype than was found in controls, while CD45RO-expressing cells were reduced. In addition, DN T cells from patients with SLE expressed significantly higher levels of HLA-DR (P = 0.006), CD28 (P = 0.05), CTLA4 (P = 0.03) and CD45RA (P = 0.05) on the cell surface than those from the CD4/8 population. Correlation of expression of the markers measured with various parameters of disease activity and severity showed that high levels of HLA-DR expression correlated with high circulating serum C3 (> 0.9 IU/ml), indicating that an activated phenotype is consistent with severe disease.

Bodman-Smith MD, Anand A, Durand V, Youinou PY, Lydyard PM. · Department of Immunology, Royal Free and University College London Medical School, London, UK. · Immunology. · Pubmed #10792496 links to  free full text

Abstract: Some gammadelta T cells express a receptor for the Fc portion of immunoglobulin G (FcgammaRIII - CD16). The relevance of this Fc receptor to gammadelta T-cell function is at present unclear. Our previous studies have shown that gammadelta T cells express activation markers in patients with rheumatoid arthritis (RA). In this study we have examined the relative proportions of CD16+ gammadelta T cells in the blood and synovial fluid of these patients compared with control blood. CD16+ gammadelta T cells from RA patients were significantly reduced in synovial fluid compared with the circulation. That this was due to blocking of antibody binding to CD16 was unlikely as treatment of blood gammadelta T cells with RA synovial fluid (known to contain immune complexes) failed to alter expression of CD16. Treatment of blood gammadelta T cells with phytohaemagglutinin in vitro, resulted in a time-dependent decrease in expression of CD16, with a concomitant increase in expression of human leucocyte antigen-DR, at the single cell level. We conclude that expression of CD16 by gammadelta T cells is lost in the synovial compartment as the result of activation.

Abrahams VM, Cambridge G, Lydyard PM, Edwards JC. · University College London, UK. · Arthritis Rheum. · Pubmed #10728755 links to  free full text

Abstract: OBJECTIVE: Small IgG rheumatoid factor immune complexes may provide the trigger for macrophage-derived tumor necrosis factor alpha (TNFalpha) production in rheumatoid arthritis. Immune complexes may bind to any of 3 IgG Fc receptors (FcgammaR). Therefore, the ability of monocyte-derived macrophages to produce TNFalpha was examined following ligation of each of the 3 human FcgammaR, using murine monoclonal antibodies (mAb) to each receptor as a model for small immune complexes. METHODS: Adhered human monocytes expressing all 3 FcgammaR were incubated with murine anti-FcgammaR mAb directed against FcgammaRI, FcgammaRII, or FcgammaRIII. Supernatants were collected at various time points and tested for the presence of TNFalpha and interleukin-1alpha (IL-1alpha) by enzyme-linked immunosorbent assay. RESULTS: The anti-FcgammaRIII mAb induced adhered human monocytes to release TNFalpha. However, F(ab)2 and Fab fragments of the anti-FcgammaRIII mAb failed to induce TNFalpha production. TNFalpha was undetectable following incubation with the anti-FcgammaRI or anti-FcgammaRII mAb. Furthermore, blocking FcgammaRI or FcgammaRII had no effect on the levels of TNFalpha released in response to the anti-FcgammaRIII mAb. Of the 3 anti-FcgammaR mAb, only anti-FcgammaRIII induced IL-1alpha production from adhered human monocytes, and this was inhibited by the presence of a neutralizing anti-TNFalpha mAb. CONCLUSION: This study suggests a dominant role for FcgammaRIIIA in the induction of both TNFalpha and IL-1alpha production by human macrophages in rheumatoid arthritis following receptor ligation by small immune complexes. The signaling of TNFalpha production may require the ligation of either 3 FcgammaRIIIA receptors or only 2 FcgammaRIIIA receptors, where one interaction must involve binding via an Fc domain. In addition, IL-1alpha production following FcgammaRIIIA ligation appears to be dependent on the presence of TNFalpha.