Beneficial brain autoimmunity?

Markesbery WR. Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Long-term behavioral and neuroendocrine alterations following chronic social stress in mice: implications for stress-related disorders. Association of education with incidence of cognitive impairment in three established populations for epidemiologic studies of the elderly. Role of the contralateral inferior frontal gyrus in recovery of language function in poststroke aphasia: a combined repetitive transcranial magnetic stimulation and positron emission tomography study. This issue of Brain contains two articles that, although coming from strikingly different backgrounds, seem to describe one common phenomenon: beneficial autoimmunity. Beneficial auto-immunity? Strict linguists would qualify this mere term as unacceptably paradoxical, in more than one sense: how can 'immunity', i.e. protection against potential danger, turn against self and cause disease, and furthermore, why should this be called 'beneficial'? Linguistics aside, the concept of beneficial autoimmunity has developed over the past decades. Initially, brain-specific T cell clones were first isolated from autoantigen-primed and subsequently even from completely normal, healthy rodents. When transferred into healthy recipients, these T cells caused severe en-cephalomyelitis (Ben-Nun et al., 1981; Schluesener and Wekerle, 1985). Later, it turned out that primates, in particular human beings, also have high numbers of autoreactive T cells in circulating blood. When activated ex vivo and re-injected into the same donor, the autoreactive T cells cause disease, as shown in monkeys (Meinl et al., 1997). But, why do we all harbour potentially pathogenic self-reactive immune cells in our immune repertoires? It is hard to accept that our self-reactive T cells just evolved to persist as vicious time bombs waiting for a trigger to detonate. Instead, could these cells be on a beneficial mission, which we still wait to appreciate fully? And, how could autoimmune T cells function favourably? In their pursuit of infectious agents, immune responses commonly create collateral damage of previously intact tissues. But at the same time, they are supportive of tissue regeneration, for example , healing of skin wounds by releasing regenerative mediators (Jameson et al., 2002). In addition, immune cells also produce neurotrophins, like brain-derived nerve growth factor (BDNF), which act in manifold ways on neural cells (Kerschensteiner et al., 1999). Thus, it is not too far-fetched to assume that under particular conditions, autoimmune T cells could help regen-eration of lesioned cells by depositing BDNF or other trophic factors. One of the new Brain papers studies the role of BDNF …