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Control of Autoreactive T Cell Activation by Immunoregulatory T Cells (Art)

  • Jean-François Bach
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 490)

Abstract

It had been known for several decades that autoimmunity does not necessarily lead to pathological manifestations. In fact, such harmless autoimmunity can be considered as physiologic since it is observed in all healthy individuals, both at the B cell level (natural autoantibodies)1 and at the T cell level (one can derive MHC class II or organ specific T cell lines from normal peripheral blood lymphocytes)2 Progression to pathogenic autoimmunity requires autoreactive B and/or T cell activation. This requirement is well illustrated by the classic double transgenic mouse experiment in which coexistence of overexpression of a target antigen (a viral protein) in the ß cells of the islets of Langerhans and overexpression of T cells specific for this antigen does not lead to diabetes without activation of the said T cells by infection with the specific virus.3 The question is thus posed of the origin and the modalities of such activation of autoreactive B or T cells in spontaneously occurring autoimmune diseases. On the other hand, it appears that the progression to clinical manifestations in these diseases is often very slow and preceded by a long phase of preclinical autoimmunity which is apparently more intense than the physiologic autoimmunity mentioned above but yet insufficient to create clinically relevant lesions. This preclinical autoimmune phase is particularly well documented in insulin-dependent diabetes mellitus (IDDM), both in the non-obese diabetic (NOD) mouse and in human disease.4 The question is to determine what are the mechanisms responsible for such a control of disease progression. Are they related to those preventing undesirable clinical expression of physiological autoimmunity? In this chapter, data will be reviewed that indicate that such mechanisms essentially involve CD4 T cells which begin to be characterized in terms of their phenotype, their autoantigen specificity, their mode of action, their genetic control and their sensitivity to environmental factors.

Keywords

Nonobese Diabetic Mouse Cyclophosphamide Treatment Costimulatory Pathway Autoimmune Polyendocrine Syndrome Natural Autoantibody 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Jean-François Bach
    • 1
  1. 1.Hôpital NeckerINSERM U 25ParisFrance

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