T cell memory specific for self and non-self antigens in rats persistently infected with Borna disease virus

Abstract

SUMMARYWe have studied CD4' Thl Tcell responses in Borna disease (BD). a virus-mediated immune disease of the central nervous system (CNS), and demonstrate the priming of virus-specific as well as autoreacti veT cells specilicf or myclin antigens in the course of viral infection. The fate of these//H'/ro generated T cells was subsequently assessed by in vitro proliferation assays with lymphocytes from different lymphoid organs of diseased animals over a long period of time. Virus-specilie T cell responses continuously decreased during the establishment of persistent infection and could no longer be detected after 5-6 months/'o.sf infectionem. when inflammatory reactions in Ihe brain had ceased. By contrast, autoantigen-specific T celts kepi their ability to mount characteristic secondary responses-although at an overall rather low level-over long periods of time: these autoreactive T cellshomed to a specihc lymphoid organ, the perithymic lymph node. Our study thus describes for the first time a complete decline of virus-specific Tcell metiiory in a persistent viral infection, and raises the question how long-lasling Tcell autoreactivity is controlled.

Autoimmunity caused by host cell protein-containing viruses

“…Paraffin-embedded section, hematoxylin-eosin staining, xl00 sponse against MBP but not against PLP or a third-party antigen (ovalbumin; Table 1), indicating that MBP-specific autosensitization had occurred. The magnitude of autoreactivity is compatible with levels of MBP-directed T cell responsiveness described in other rat models of virus-induced CNS autoimmunity, such as coronavirus-induced encephalopathy [24], subacute measles encephalomyelitis [13], or in Borna virus disease [21]. Adoptive transfer of these T cells after in vitro restimulation (5x107 cells transferred cells/animal) resulted in typical EAElike symptoms in recipient Lewis rats (weight loss, unsteady gait and loss of tail tonus; symptoms were found in eight out of ten animals tested).…”

“…to manifest clinical signs of an autoimmune disease. In fact, experimental models of virus-mediated autoimmune diseases are still nowadays the only satisfying models to exemplify naturally occurring induction of autoimmunity [5,13,21,24]. However, the exact mechanisms leading to the breakdown of natural tolerance in the course of viral infections remain largely obscure.…”

B‐Cell Activation by Superstimaulatory Influenza Virus Hemagglutinin: A Pathogenesis for Autoimmunity?

“…In fact, experimental models of vims-mediated autoimmune diseases are still the only satisfying models to exemplify naturally occurring induction of autoimmunity (Zinkemagei et al 1991, Fujinami & Oldstone 1985, Watanabe et a!. 1983, Srinivasappa 1988, Rott et al 1993, ter Meulen & Liebert 1993. Furthermore, in a number of so-called T-cell mediated autoimmune diseases' (e.g.…”

The Challenge of Assessing Mild Neuroinflammation in Severe Mental Disorders

“…These findings suggested the possibility that both these clinical syndromes, neurological syndromes of lymphocytic meningencephalitis and psychiatric syndromes (SMDs including various types of broadly defined affective and schizophrenic spectrum psychoses) were caused by an underlying infection by BDV, in some cases with neurological and psychiatric syndromes even clustering in families (35). From experimental research, two different pathomechanisms underlying the clinical syndromes appeared plausible mechanisms (18,(36)(37)(38)(39): acute mild localized (preferential brain region involved was the limbic system) infectious encephalitis or autoimmunity triggered by the BDV infection (40), and thus both pathomechanisms might in principle have the potential to induce a spectrum of psychiatric syndromes depending from a variety of known contributive factors including immune status of the infected, age, genes and others [compare (18,36)]. However, non-deadly but clinically relevant brain infection or CNS autoimmunity or ME was difficult to prove in vivo, not least from ethical reasons.…”