Neuroimmunodegeneration: do neurons and T cells use common pathways for cell death?

Abstract

In syndromes of pediatric neuroimmunodegeneration (NID), certain neurons and T cells degenerate and disappear during early development at an accelerated rate without alerting the peripheral immune cells. Current studies of some of these NID syndromes suggest that the primary cause of neuronal and T cell death is an imbalanced cytokine signaling system with a dysfunctional redox status, and that the loss of T cells and neurons may be secondary to impaired functions of their accessory supportive cells. These dysfunctions include inappropriate production of developmental cytokines, inadequate secretion of reductants, and disregulation of excitotoxic amino acid metabolism. Two examples of pediatric NID in humans are ataxia telangiectasia and pediatric human immunodeficiency virus infection. An animal model is retrovirus-induced T and neuronal cell loss in neonatal mice infected with a neuroimmunopathogenic mutant, ts1, of the Moloney murine leukemia virus. Because both thymic and neuronal components share many growth factors and developmental signals, it is likely that disregulation of these signals would lead to concomitant dysfunction of neuronal and thymic cells. In this review, we focus on the pathogenic mechanisms involved in these developmental NID syndromes with the objective of identifying common pathogenic factors and pathways responsible for the concurrent losses of both neurons and T cells.