Journal of Neuroimmunology 106 (2000) 189–197 www.elsevier.com / locate / jneuroin Autoimmune T cells retard the loss of function in injured rat optic nerves a,b a a a b b Gila Moalem , Eti Yoles , Raya Leibowitz-Amit , Shir Muller-Gilor , Felix Mor , Irun R. Cohen , a, * Michal Schwartz a The Weizmann Institute of Science, Department of Neurobiology, 76100 Rehovot, Israel b The Weizmann Institute of Science, Department of Immunology, 76100 Rehovot, Israel Received 11 January 2000; accepted 7 February 2000 Abstract We recently demonstrated that autoimmune T cells protect neurons from secondary degeneration after central nervous system (CNS) axotomy in rats. Here we show, using both morphological and electrophysiological analyses, that the neuroprotection is long-lasting and is manifested functionally. After partial crush injury of the rat optic nerve, systemic injection of autoimmune T cells specific to myelin basic protein significantly diminished the loss of retinal ganglion cells and conducting axons, and significantly retarded the loss of the visual response evoked by light stimulation. These results support our challenge to the traditional concept of autoimmunity as always harmful, and suggest that in certain situations T cell autoimmunity may actually be beneficial. It might be possible to employ T cell intervention to slow down functional loss in the injured CNS.  2000 Published by Elsevier Science B.V. All rights reserved. Keywords: Autoimmunity; CNS; Injury 1. Introduction cellular homeostasis, excitotoxicity, local production of agents harmful to nerve cells, and a loss of trophic support Axonal injury in the mammalian central nervous system from targets, all of which result in secondary neuronal loss. (CNS) initiates a process of axonal degeneration at the The proposed mechanisms of secondary degeneration have injury site, usually leading to failure of the damaged fibers served as a basis for the development and evaluation of to regrow and reconnect, and the eventual death of the various pharmacological interventions for the treatment of corresponding cell bodies (Ramon y Cajal, 1959). In CNS injuries. The therapeutic approach of preventing or addition, fibers that have not sustained direct injury but are diminishing the secondary degeneration accompanying located in the vicinity of the injured neurons will, unless CNS trauma is termed neuroprotection (Faden and Sal- adequately treated, undergo secondary degeneration zman, 1992; McIntosh, 1993; Smith et al., 1995). (Faden, 1993; Lynch and Dawson, 1994; Yoles and T cells are important players in the adaptive arm of the Schwartz, 1998). This progressive spread of damage immune system. T cells respond to specific antigens results from a process that begins within minutes of injury through interactions of their specific antigen receptor with and continues for days or weeks (Faden, 1993; Yoles and the antigen presented by major histocompatibility complex Schwartz, 1998). Among the injury-related mechanisms molecules and a group of costimulatory molecules. When that might underlie the post-traumatic spread of damage activated, they can kill their target cells or produce are biochemical and metabolic changes in oxygen and cytokines that activate or suppress the growth, movement, glucose utilization, energy state, lipid-dependent enzymes, or differentiation of other cells. Thus, T cells play a critical free radicals, eicosanoids, tissue ions, biogenic amines, part in the protection of tissues against foreign invaders as endogenous opioids, and excitatory amino acids (Hovda et well as in tissue maintenance. al., 1991; Yoshino et al., 1991; Yoles et al., 1992; Faden, Immune responses in the CNS are relatively restricted, 1993; Liu et al., 1994). These changes cause alterations in resulting in the status of the CNS as an immune-privileged site (Streilein, 1995). The unique nature of the communi- cation between the CNS and the immune system can be *Corresponding author. Tel.: 1972-8-934-2467; fax: 1972-8-934- observed, for example, in the dialog between the CNS and 4131. E-mail address: bnschwar@weizmann.weizmann.ac.il (M. Schwartz) T cells. In the CNS, under normal conditions activated T 0165-5728 / 00 / $ – see front matter  2000 Published by Elsevier Science B.V. All rights reserved. PII: S0165-5728(00)00240-X