Regulation of interleukin 2 receptors on T cells from multiple sclerosis patients.

DeFreitas, Elaine; Sandberg‐Wollheim, Magnhild; Schonely, Kathy; Boufal, Margaret; Koprowski, Hilary

doi:10.1073/pnas.83.8.2637

Cited by 37 publications

(7 citation statements)

References 26 publications

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“…Nonetheless, in our patients the main immune effects of IFN-β were as expected. Indeed, the proliferative response of Teff after 12 months of IFN-β treatment was impaired, and the increased frequency of CD4+CD25 medium T cells observed in patients at baseline, which is a frequent immunological abnormality occurring in MS patients and indicates CD4+ Th1 lymphocyte activation [41,42,43], was significantly reduced, even if not completely reverted, after 12 months of treatment with IFN-β, in agreement with previous reports [41,44]. …”

Section: Discussionsupporting

confidence: 79%

Dopaminergic Modulation of CD4+CD25<sup>high</sup> Regulatory T Lymphocytes in Multiple Sclerosis Patients during Interferon-β Therapy

Cosentino

Zaffaroni²,

Trojano

et al. 2012

Neuroimmunomodulation

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Objective: We investigated dopaminergic inhibition of CD4+CD25^high regulatory T lymphocytes (Treg) in relapsing-remitting multiple sclerosis (MS) patients treated with interferon (IFN)-β. Methods: MS patients were prospectively studied at baseline and during 1 year of IFN-β, and compared with healthy controls (HCs). Treg were separated by immunomagnetic sorting and the effect of dopamine (DA) on Treg was assessed in coculture experiments with homologous effector T lymphocytes (Teff). Tyrosine hydroxylase (TH), dopaminergic receptors (DR) D3 and D5, and forkhead box protein P3 (FoxP3) mRNA were assessed by real-time PCR. Circulating CD4+ T cell subsets were assessed by flow cytometry. Results: In coculture experiments, Treg inhibition of Teff proliferation was reduced by DA in HCs and completely abolished in MS patients at baseline. However, in patients after 12 months of IFN-β, Teff proliferation was impaired and DA had no more effect on Treg. In comparison to cells from HCs, Treg from MS patients at baseline had increased mRNA for DR D5 and TH (but not for DR D3). During treatment with IFN-β, both DR D5 and TH mRNA decreased down to values lower than those of cells from HCs. In comparison to HCs, MS patients had a higher frequency of circulating Treg, both at baseline and after IFN-β, while FoxP3 mRNA levels in Treg were similar in patients and HCs and did not show major changes during IFN-β. Conclusions: Dopaminergic inhibition of Treg in MS patients is suppressed during IFN-β treatment. Treg play a key role in the suppression of autoimmunity, thus the effect may have a therapeutic repercussion.

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Section: Discussionsupporting

confidence: 79%

Dopaminergic Modulation of CD4+CD25<sup>high</sup> Regulatory T Lymphocytes in Multiple Sclerosis Patients during Interferon-β Therapy

Cosentino

Zaffaroni²,

Trojano

et al. 2012

Neuroimmunomodulation

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“…In several reports on lesional tissue in MS, the CD8+ cell predominance was much more impressive than in our birds, but the general trend seems to be comparable in patients and in the quailchicken chimeras. Similarly, the lack of B cells in the lesion al tissue of the chimeras is comparable to the scarcity of B cells in the lesions of MS [17].…”

Section: Discussionmentioning

confidence: 65%

Morphological Studies on Avian Spinal Cord Chimeras

Saitô

Sugisaki

Yang

et al. 1996

Int Arch Allergy Immunol

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Spinal cord chimeras were constructed by orthotopic grafting of quail embryonal neutral folds, neural crest and neural tube into chicken embryos. The spinal cord xenografts were accepted for varying lengths of time, but most chimeras eventually rejected the quail transplant. This was associated with perivenular cuffing and demyelination with preservation of most neurons, as well as clinical neurological symptoms. Twenty-four chimeras were studied to delineate the time of first appearance of glial deposits of immunoglobulin and to identify the subpopulations of T cells in spinal cord infiltrates. The results suggested that deposits of immunoglobulins on glial elements preceded inflammatory cell infiltration. The perivenular cuffs consisted predominantly of T cells and showed a preponderance of CD8- over CD4-positive cells (CD4/CD8 ratios around 0.6). Further, CD4+ cells were found almost exclusively in the central portions of the infiltrate, with the periphery consisting almost only of CD8+ cells. The diffuse cellular infiltrate of the parenchyme contained T and plasma cells. The T cells were almost exclusively CD8+. Plasma cells were seen only at the outer borders of the cuffs and dispersed throughout the quail-derived spinal cord tissue. It seemed that rejection of quail-derived melanocytes in feathers (‘quail-like feathers’), described by us earlier, often preceded neurological symptoms and showed a histopathological pattern comparable to spinal cord lesions, i.e., predominantly peri-vascular cuffing. In preliminary studies, enhancement of disease by immunization with quail organ suspension and decreased intensity of disease by combined immunosuppressive treatment with FK 506 and cycylophosphamide were suggested. The data presented here are compatible with the hypothesis that rejection of CNS quail tissue by chimeras is preceded in the periphery by rejection of melanocytes in segments of skin and in feathers, and that the spinal cord rejection relies on xenoantibodies and on cytotoxic as well as delayed hypersensitivity-type T cells. Finally, these data strengthen the analogy between the histopathologic presentation and immune effector composition of the xenograft rejection lesions in the chimeras and the plaques seen in patients with multiple sclerosis.

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“…The analysis of CSF from non-inflammatory nonneurological patients revealed little LAF activity, in contrast with the findings of Gorczynski and Keystone [16], who found considerable IL-1 like activity in fractionated and five-fold concentrated CSF from patients with degenerative neck or back disease. Accordingly, De Freitas et al [8] noted a prolonged expression of IL-2 receptors and responsiveness to IL-2 in T-cells from both MS blood and CSF. In normal healthy control serum, LAF activity was detectable even without fraction.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte activating factor activity in the serum and cerebrospinal fluid of patients with multiple sclerosis

et al. 1990

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Serum and cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS), patients with other (non-inflammatory) neurological diseases (OND), patients with non-inflammatory non-neurological diseases, and normal controls were assayed for lymphocyte activating factor (LAF) activity by thymocyte costimulation. LAF activity was detected in normal control sera, which did not differ significantly in this respect from MS or OND patient sera. Not were there significant differences by stage of MS (chronic progressive MS, MS in relapse and MS in remission) or between MS patients and the non-inflammatory non-neurological controls. Almost all the CFSs assayed presented lower values than did the corresponding sera. Serum and CSF after fractionation showed no significant increase in LAF activity except in the 2 MS patients in remission. From these data it may be assumed that LAF activity does not necessarily correspond to the clinical phase of MS. The possible role of LAF activity as a marker of MS progression has yet to be determined.

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Regulation of interleukin 2 receptors on T cells from multiple sclerosis patients.

Cited by 37 publications

References 26 publications

Dopaminergic Modulation of CD4+CD25<sup>high</sup> Regulatory T Lymphocytes in Multiple Sclerosis Patients during Interferon-β Therapy

Dopaminergic Modulation of CD4+CD25<sup>high</sup> Regulatory T Lymphocytes in Multiple Sclerosis Patients during Interferon-β Therapy

Morphological Studies on Avian Spinal Cord Chimeras

Lymphocyte activating factor activity in the serum and cerebrospinal fluid of patients with multiple sclerosis

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