showing 8 related works from this author
Myelin-specific T cells also recognize neuronal autoantigen in a transgenic mouse model of multiple sclerosis
2008
T-cell recognition of autoantigens is important in the development of autoimmune disease. Now, Hartmut Wekerle and his colleagues demonstrate that organ-specific autoimmune responses may be driven by T cells that simultaneously respond to two different autoantigens found within the same target tissue. We describe here the paradoxical development of spontaneous experimental autoimmune encephalomyelitis (EAE) in transgenic mice expressing a myelin oligodendrocyte glycoprotein (MOG)-specific T cell antigen receptor (TCR) in the absence of MOG. We report that in Mog-deficient mice (Mog−/−), the autoimmune response by transgenic T cells is redirected to a neuronal cytoskeletal self antigen, neur…
Cutting edge: Multiple sclerosis-like lesions induced by effector CD8 T cells recognizing a sequestered antigen on oligodendrocytes.
2008
Abstract CD8 T cells are emerging as important players in multiple sclerosis (MS) pathogenesis, although their direct contribution to tissue damage is still debated. To assess whether autoreactive CD8 T cells can contribute to the pronounced loss of oligodendrocytes observed in MS plaques, we generated mice in which the model Ag influenza hemagglutinin is selectively expressed in oligodendrocytes. Transfer of preactivated hemagglutinin-specific CD8 T cells led to inflammatory lesions in the optic nerve, spinal cord, and brain. These lesions, associating CD8 T cell infiltration with focal loss of oligodendrocytes, demyelination, and microglia activation, were very reminiscent of active MS le…
Thymus-derived regulatory T cells are positively selected on natural self-antigen through cognate interactions of high functional avidity
2016
Regulatory T (Treg) cells expressing Foxp3 transcripton factor are essential for immune homeostasis. They arise in the thymus as a separate lineage from conventional CD4+Foxp3- T (Tconv) cells. Here, we show that the thymic development of Treg cells depends on the expression of their endogenous cognate self-antigen. The formation of these cells was impaired in mice lacking this self-antigen, while Tconv cell development was not negatively affected. Thymus-derived Treg cells were selected by self-antigens in a specific manner, while autoreactive Tconv cells were produced through degenerate recognition of distinct antigens. These distinct modes of development were associated with the expressi…
Consensus nomenclature for CD8(+) T cell phenotypes in cancer
2015
International audience; Whereas preclinical investigations and clinical studies have established that CD8+ T cells can profoundly affect cancer progression, the underlying mechanisms are still elusive. Challenging the prevalent view that the beneficial effect of CD8+ T cells in cancer is solely attributable to their cytotoxic activity, several reports have indicated that the ability of CD8+ T cells to promote tumor regression is dependent on their cytokine secretion profile and their ability to self-renew. Evidence has also shown that the tumor microenvironment can disarm CD8+ T cell immunity, leading to the emergence of dysfunctional CD8+ T cells. The existence of different types of CD8+ T…
Classification of current anticancer immunotherapies.
2014
© 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Neurons as targets for T cells in the nervous system
2013
International audience; Accumulating evidence shows that T cells penetrate the central nervous system (CNS) parenchyma in several autoimmune, infectious, and degenerative neurological diseases. The structural and functional consequences for CNS neurons of their encounter with activated T cells have been investigated in several experimental systems, including ex vivo co-cultures, electrophysiology, and in vivo imaging. Here, we review the modalities of neuron/T cell interactions. We substantiate the contention that T cells are directly responsible for neuronal damage in a large number of neurological diseases and discuss mechanisms of neuronal damage mediated by distinct T cell subsets, the …
Innate and adaptive immune responses in the CNS.
2015
Almost every disorder of the CNS is said to have an inflammatory component, but the precise nature of inflammation in the CNS is often imprecisely defined, and the role of CNS-resident cells is uncertain compared with that of cells that invade the tissue from the systemic immune compartment. To understand inflammation in the CNS, the term must be better defined, and the response of tissue to disturbances in homoeostasis (eg, neurodegenerative processes) should be distinguished from disorders in which aberrant immune responses lead to CNS dysfunction and tissue destruction (eg, autoimmunity). Whether the inflammatory tissue response to injury is reparative or degenerative seems to be depende…
ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis.
2018
Background and purpose: Multiple sclerosis (MS) is a complex disease of the central nervous system. As new drugs are becoming available, knowledge on diagnosis and treatment must continuously evolve. There is therefore a need for a reference tool compiling current data on benefit and safety, to aid professionals in treatment decisions and use of resources across Europe. The European Committee of Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have joined forces to meet this need. The objective was to develop an evidence-based clinical practice guideline for the pharmacological treatment of people with MS to guide healthcare professionals in…