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Targeting pathogenic T helper cell memory
  1. Hyun-Dong Chang,
  2. Andreas Radbruch
  1. Deutsches Rheuma-Forschungszentrum Berlin, a Leibniz Institute, Berlin, Germany
  1. Correspondence to Andreas Radbruch, Deutsches Rheuma-Forschungszentrum Berlin, a Leibniz Institute, Charitéplatz 1, 10117 Berlin, Germany; radbruch{at}drfz.de

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Immunity to pathogens, once encountered, is one of the most obvious manifestations of the adaptive immune system. In principle, immunity can result from a chronic immune reaction to persistent antigen, or from immunological memory for the antigen, a memory maintained long term in the absence of the antigen. This was already observed in ancient times, and has led to the development of vaccination as the most successful medical treatment available today. Yet, the molecular, cellular and systemic basis of immunological memory is still poorly understood. The generation of memory cells from their precursors, the lifestyle of memory cells, their maintenance, their reactivation and their differentiation potential are still enigmatic. With respect to autoantigens, persistent pathogens and allergens, immunological memory can become detrimental, inducing and maintaining immunopathology and chronic inflammation, posing a major challenge for the treatment of, for example, autoimmunity. Immunological memory is imprinted, does not depend on antigenic stimulation, and functions independently of proliferation, properties which make it refractory to physiological regulation and rigorous therapeutic immunosuppression. Complete immune ablation followed by the regeneration of a juvenile immune system from stem cells has led to treatment-free remission in patients with autoimmune diseases such as systemic lupus erythematosus, multiple sclerosis or rheumatoid arthritis, demonstrating that, in principle, curative treatment is possible. The concomitant loss of all protective immunity and the resulting susceptibility to lethal opportunistic infections, however, calls for the development of a more specific therapeutic approach targeting only those memory cells perpetuating autoimmune inflammation. This requires a better understanding of the immunological memory providing protective and pathological immunity.

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CD4 Th lymphocytes are distinguished by different lineages based on the cytokines they express and the resulting effector function. Once activated, Th lymphocytes can generate a memory for the cytokines they were instructed to express, epigenetically imprinting distinct cytokine loci and stably …

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