Anne Cooke - Academia.edu (original) (raw)

Papers by Anne Cooke

The Journal of Immunology

In vitro culture of murine spleen cells in FCS without prior immunization or allogeneic stimulati... more In vitro culture of murine spleen cells in FCS without prior immunization or allogeneic stimulation leads to the development of spontaneous cytotoxicity. This cytotoxicity is not H-2 restricted and can affect any subsequent in vitro assays using syngeneic cells, especially if those assays include prolonged culture in FCS. Studies on murine spleen cells cultured in NMS, however, led to the detection of a suppressor system that did not display cytotoxic effects. Furthermore, it was found that this suppression, in contrast to the cytotoxicity and suppression generated during culture in FCS, was not sensitive to CYA. The suppressor cell may be an effector or an inducer of suppression and is sensitive to treatment with anti-Thy-1.2 and complement. It is suggested that some in vitro suppression is really due to cytotoxicity that may be directed toward FCS determinants adsorbed onto syngeneic targets.

Diabetologia, 1987

The aberrant expression of Class-II molecules on pancreatic B cells in Type I (insulin-dependent)... more The aberrant expression of Class-II molecules on pancreatic B cells in Type I (insulin-dependent) diabetes is still a matter of debate. In order to verify if Class-II molecules are expressed on islet cells in the NOD mouse we have studied 21 female mice of different ages (5 to 22 weeks). Serial cryostat pancreas sections were stained with monoclonal rat antibodies against Class-II antigens (P7/7) and the IL2 receptor (AMT-13). Our results show no Class-II expression by endocrine cells at any age, whereas about 25-32% of mononuclear cells infiltrating the islets were Class-II positive , and only 6-9% were IL2 receptor positive. No staining, except of occasional tissue macrophages, was observed in the pancreas of BALB/c, CBA or B 10.SCSN mice. Our data are in contrast with those recently published and therefore the reality of expression of Class-II molecules by islet cells of NOD mice should be viewed with caution.

Gene Therapy, 2018

We report the restoration of euglycaemia in chemically induced diabetic C57BL/6 mice and spontane... more We report the restoration of euglycaemia in chemically induced diabetic C57BL/6 mice and spontaneously diabetic Non Obese Diabetic (NOD) mice by intravenous systemic administration of a single-stranded adeno-associated virus (ssAAV2/8) codon optimised (co) vector encoding furin cleavable human proinsulin under a liver-specific promoter. There were no immunological barriers to efficacy of insulin gene therapy in chemically induced C57BL/6 mice, which enjoyed long-lasting correction of hyperglycaemia after therapy, up to 250 days. Euglycaemia was also restored in spontaneously diabetic NOD mice, although these mice required a 7-10-fold higher dose of vector to achieve similar efficacy as the C57BL/6 mice and the immunodeficient NOD scid mice. We detected CD8 + T cell reactivity to insulin and mild inflammatory infiltration in the livers of gene therapy recipient NOD mice, neither of which were observed in the treated C57BL/6 mice. Efficacy of the gene therapy in NOD mice was partially improved by targeting the immune system with anti-CD4 antibody treatment, while transfer of NOD mouse AAV2/8-reactive serum to recipients prevented successful restoration of euglycaemia in AAV2/8-HLP-hINSco-treated NOD scid mice. Our data indicate that both immune cells and antibodies form a barrier to successful restoration of euglycaemia in autoimmune diabetic recipient mice with insulin gene therapy, but that this barrier can be overcome by increasing the dose of vector and by suppressing immune responses.

Journal of Clinical Investigation, 1995

CD4' T cell lines were generated from the spleens of diabetic NOD mice against crude membrane pre... more CD4' T cell lines were generated from the spleens of diabetic NOD mice against crude membrane preparations derived from a rat insulinoma. Adoptive transfer of these lines into neonatal mice confirms that overt diabetes is induced by v-IFN-secreting Thl cells, whereas transfer of IL-4-secreting Th2 cells resulted in a nondestructive peni-islet insulitis. Analysis of the antigens recognized by individual T cell clones from the Thl line included reactivity against an insulinoma membrane fraction enriched in proteins of-38 kD. Immune responses to the same antigen preparation have been associated with T cell clones derived from human insulin-dependent diabetes mellitus. The specificity of Th2 cells includes reactivity to a fraction enriched in proteins of 30 kD. The data suggest that in insulin-dependent diabetes mellitus the balance between fB cell destruction, associated with intra-islet infiltration, and nondestructive (potential protective) peri-islet insulitis may depend on both the antigens recognized, and the prevailing cytokine environment. (J.

Immunology, 1999

The drug Linomide is an immunomodulator showing marked down‐regulation of several experimental au... more The drug Linomide is an immunomodulator showing marked down‐regulation of several experimental autoimmune diseases. In this study, its effect on three different experimental models of thyroid disease and on spontaneous infiltration of salivary glands (sialoadenitis), was investigated. Although very effective at preventing thyroid infiltrates in mice immunized with mouse thyroglobulin and complete Freund’s adjuvant and in spontaneous models of thyroiditis and sialoadenitis, it completely failed to modify experimental autoimmune thyroiditis (EAT) induced in mice immunized with mouse thyroglobulin and lipopolysaccharide. There was no significant shift in the observed isotypes of anti‐mouse thyroglobulin antibodies and only anti‐mouse thyroglobulin antibodies in the spontaneous model were completely down‐modulated by the drug. One surprising fact to emerge was that Linomide‐treated donor mice, although protected from thyroid lesions themselves, were still able to transfer EAT showing th...

Clinical and Experimental Immunology, 2008

SUMMARYAdjuvant arthritis, induced by injections of Freund's complete adjuvant into the footp... more SUMMARYAdjuvant arthritis, induced by injections of Freund's complete adjuvant into the footpads of some rat strains, has been recognized as a useful animal model for many years. There has, however, been notable lack of success in reproducing this model in other species. We now describe the development of adjuvant arthritis in healthy strain mice approximately 2 months after injection of Freund's complete adjuvant. Although the clinical appearance of the mice and the joint histopathology closely resemble the adjuvant arthritis reported in the rat. we were unable to detect rheumatoid factor in sera from the affected animals. In parallel studies of T cell proliferation, affected animals responded to some mycobaclcrial antigens but not to the 65-kD heat shock protein of Mycobacterium tuberculosis, suggesting that some other epitope is important in the development of the disease.

Archives of Oral Biology, 1992

This antigen was examined in rats of different ages (new-born, 3, 5, 7, 10, 12 and 14 days after ... more This antigen was examined in rats of different ages (new-born, 3, 5, 7, 10, 12 and 14 days after birth and adult) by immunofluorescence and immunoelectron microscopy. Changes in each kind of salivary gland when graft versus host disease was induced in recipient rats were also investigated. Monoclonal antibodies (HAM 2 or OX 18) specific to rat MHC class I antigen were used and these were detected by FITC-conjugated anti-mouse immunoglobulin. With HAM 2, MHC class I antigen in the submandibular gland was mostly located in the secretory duct cells; this expression was first found 10 days after birth. The antigen was found on the cell surfaces of the secretory duct cells by immunoelectron microscopy. With OX 18, MHC class I antigen was mainly found in the secretory duct cells, but weak expression was also found in the acinar cells. Localization of the antigen, by HAM 2 and OX 18 was less evident in the secretory duct cells of parotid and sublingual glands. When graft versus host disease was induced, MHC class I antigen (HAM 2) was observed in both acinar and secretory duct cells of the submandibular gland.

European Journal of Immunology, Apr 1, 2009

Schistosoma mansoni soluble egg antigens (SEA) profoundly regulate the infected host's immune... more Schistosoma mansoni soluble egg antigens (SEA) profoundly regulate the infected host's immune system. We previously showed that SEA prevents type 1 diabetes in NOD mice and that splenocytes from SEA‐treated mice have reduced ability to transfer diabetes to NOD.scid recipients. To further characterize the mechanism of diabetes prevention we examined the cell types involved and showed that CD25+ T‐cell depletion of splenocytes from SEA‐treated donors restored their ability to transfer diabetes. Furthermore, SEA treatment increased the number and proportional representation of Foxp3+ T cells in the pancreas of NOD mice. We have used in vitro systems to analyze the effect of SEA on the development of NOD Foxp3+ T cells. We find that SEA can induce Foxp3 expression in naïve T cells in a TGF‐β‐dependent manner. Foxp3 induction requires the presence of DC, which we also show are modified by SEA to upregulate C‐type lectins, IL‐10 and IL‐2. Our studies show that SEA can have a direct effect on CD4+ T cells increasing expression of TGF‐β, integrin β8 and galectins. These effects of SEA on DC and T cells may act in synergy to induce Foxp3+ Treg in the NOD mouse.

Immunology

To define the interactions between self thyroglobulin (Tg)-reactive T and B we co-cultured enrich... more To define the interactions between self thyroglobulin (Tg)-reactive T and B we co-cultured enriched B cells taken from rat or mouse Tg-primed mice with major histocompatibility complex (MHC) class II-restricted T-cell lines specific for iodinated determinants on self-Tg, or hybridomas derived from those lines. Using two clonally distinct T-cell hybridomas, ADA2 and CH9, in vitro help for Tg autoantibody responses was observed using mouse (M)Tg-primed B cells and a 100 ng/ml MTg challenge. Using rat Tg-primed B cells and the same conditions, only CH9 provided help, indicating that the fine specificity of B cells influences their ability to interact with specific anti-Tg T-cell clones. In contrast to T-cell hybridomas, their parent T-cell lines MTg9B3 and MTg12B suppressed Tg autoantibody responses in vitro, although they augmented bystander proliferation of unprimed B cells. The MTg12B cells also (i) diminished the survival of Tg-primed B cells, and (ii) inhibited the proliferation o...

Immunology Today, 1983

Ehrlich was rarely given to trivial pronouncements and his recognition of the central importance ... more Ehrlich was rarely given to trivial pronouncements and his recognition of the central importance of the distinction between self and non-self by the immune system, embodied in his concept of 'horror autotoxicus'l, is no exception. This is despite the apparent paradox of the idiotype network in which antibodies recognize self-epitopes on other antibody molecules or antigen receptors as part of the normal process of immune regulation 2. In this review Anne Cooke and her colleagues examine the possible factors which may contribute to the breakdown of self-tolerance and the establishment of autoimmune states.

Immunology, 1987

Several immunological responses of the spontaneously diabetic BB rat colony in Edinburgh designat... more Several immunological responses of the spontaneously diabetic BB rat colony in Edinburgh designated (BB/E) have been studied. The proliferative responses to Con A and LPS, ability to make IL-2 and to show NK activity have been studied using diabetic and non-diabetic BB/E rats and normal Wistar rats. Our data suggest that the diabetic animals in the BB/E colony do not have marked deficiencies in any of these parameters. Lymphopenia and depressed T-cell responses do not appear to be a prerequisite for the development of diabetes in the BB/E colony.

Immunology Methods Manual, 1996

Mucosal Immunology, 2013

Bacterial-induced intestinal inflammation is crucially dependent on interleukin (IL)-23 and is as... more Bacterial-induced intestinal inflammation is crucially dependent on interleukin (IL)-23 and is associated with CD4 þ T helper type 1 (Th1) and Th17 responses. However, the relative contributions of these subsets during the induction and resolution of colitis in T-cell-sufficient hosts remain unknown. We report that Helicobacter hepaticus-induced typhlocolitis in specific pathogen-free IL-10 À / À mice is associated with elevated frequencies and numbers of large intestinal interferon (IFN)-c þ and IFN-c þ IL-17A þ CD4 þ T cells. By assessing histone modifications and transcript levels in IFN-c þ , IFN-c þ IL-17A þ , and IL-17A þ CD4 þ Tcells isolated from the inflamed intestine, we show that Th17 cells are predisposed to upregulate the Th1 program and that they express IL-23R but not IL-12R. Using IL-17A fate-reporter mice, we further demonstrate that H. hepaticus infection gives rise to Th17 cells that extinguish IL-17A secretion and turn on IFN-c within 10 days post bacterial inoculation. Together, our results suggest that bacterial-induced Th17 cells arising in disease-susceptible hosts contribute to intestinal pathology by switching phenotype, transitioning via an IFN-c þ IL-17A þ stage, to become IFN-c þ ex-Th17 cells.

Journal of Biomedicine and Biotechnology, 2010

We have shown thatSchistosoma mansoniegg soluble antigen (SEA) prevents diabetes in the nonobese ... more We have shown thatSchistosoma mansoniegg soluble antigen (SEA) prevents diabetes in the nonobese diabetic (NOD) mouse inducing functional changes in antigen presenting cells (APCs) and expanding T helper (Th) 2 and regulatory T cell (Treg) responses. A Th2 response toS. mansoniinfection or its antigens is key to both the establishment of tolerance and successfully reproduction in the host. More recently we demonstrated that SEA treatment upregulates bioactive TGFβon T cells with consequent expansion ofFoxp3+Tregs, and these cells might be important in SEA-mediated diabetes prevention together with Th2 cells. In this study we profile further the phenotypic changes that SEA induces on APCs, with particular attention to cytokine expression and markers of macrophage alternative activation. Our studies suggest that TGFβfrom T cells is important not just for Treg expansion but also for the successful Th2 response to SEA, and therefore, for diabetes prevention in the NOD mouse.

Annals of the Rheumatic Diseases, 1986

Pathological changes in the connective tissue of the limbs of MRL/1 mice are described. Focal inf... more Pathological changes in the connective tissue of the limbs of MRL/1 mice are described. Focal infiltrates of polymorphs or large mononuclear cells, or both, were seen both in synovial lining and subcutaneous tissue. Infiltrates were associated with vasculitis in some cases. Deposits of amorphous material were seen in and around joints and in foot pads. The material was more particulate and refractile than typical 'fibrinoid' and showed a positive Feulgen reaction. It was not surrounded by palisading cells and when seen in synovial tissue was not usually associated with changes in synovial lining cells. No obvious difference was seen between intra-articular and extra-articular lesions. Lesions in subcutaneous tissue occurred exclusively in the foot pads. Lymphocyte infiltration was not prominent at any site and no follicle formation was seen. Of two colonies studied, only one showed a significant increase in lining cell numbers in synovial tissue. Exercised animals had a similar distribution and severity of disease to those of matched controls. All lesions described were distinguishable from non-specific inflammatory lesions in normal control mice and MRL/+ + mice on assessment of unmarked sections. The relation between these connective tissue lesions and the changes found in human chronic synovitis is discussed.