Experimental allergic encephalomyelitis in the absence of a classical delayed-type hypersensitivity reaction. Severe paralytic disease correlates with the presence of interleukin 2 receptor-positive cells infiltrating the central nervous system.

Abstract

One characteristic of experimental allergic encephalomyelitis (EAE) in all species is the presence of a considerable leukocyte infiltrate in the central nervous system (CNS). By adoptive transfer of EAE into irradiated or nonirradiated Lewis strain rats we now show that the bulk (greater than 90%) of infiltrating cells in the CNS are superfluous to the induction of disease, as lethally irradiated recipients, despite having very few infiltrating cells in the CNS, acquire severe paralytic EAE. The reduction in the level of infiltration in irradiated recipients is selective, however, as both irradiated and nonirradiated diseased animals have very similar numbers of cells expressing IL-2-R. Disease in irradiated recipient animals is associated with substantial submeningeal hemorrhage in the spinal cord and brain stem and similar hemorrhages are found in recipients rendered leukopenic with cytotoxic drugs. Clinical signs of disease and hemorrhage are preventable, however, by administration to the recipient rats of mAbs specific for the CD4 antigen. Classic delayed-type hypersensitivity (DTH) reactions are transferable with the same cells that produce EAE in both irradiated and nonirradiated recipient rats, but such transfer of DTH is observed only in nonirradiated recipient animals and not in irradiated rats. Collectively, the findings reported herein support the conclusion that the paralysis characteristic of acute EAE is mediated by the direct action of very small numbers of activated CD4+ lymphocytes that infiltrate the CNS and produce their effects by inducing vascular damage. The findings are not consistent with reports that the lesions in EAE are produced by a classic DTH reaction.

Breakdown of the Blood-Retinal Barrier Induced by Activated T Cells of Nonneural Specificity

“…The segments of vessels in which inflammatory cells accumulate might contain high concentrations of cytokines and chemokines including interleukin-1 and tumor necrosis factor-␣ and may therefore exhibit localized changes in permeability. 3 Our data support an earlier speculation from EAE studies 25 that intravascular injection of T cells alone may have the capacity to cause CNS vascular damage directly.…”

Apoptosis of αβ T lymphocytes in the nervous system in experimental autoimmune encephalomyelitis: Its possible implications for recovery and acquired tolerance

“…Since only a minority of the infiltrating cells in the CNS in EAE are MBP-specific [17,18], it is possible that all the apoptotic T cells that we observe are autoreactive. Selective elimination by apoptosis within the spinal cord may contribute to the low yield of MBP-specific cells in lymphocytes extracted from the spinal cord of rats with acute MBP-EAE [19].…”

Inflammatory cells, microglia and MHC class II antigen-positive cells in the spinal cord of Lewis rats with acute and chronic relapsing experimental autoimmune encephalomyelitis

“…This might cause greater numbers of T lymphocytes to remain in the CNS of CsA treated rats in remission after the first episode of CR-EAE than in rats that have recovered from acute EAE; however, with the exception of TCRαβ + cells, which were more frequent in the rats recovered from acute EAE, there was no significant difference. Because only a minority of the T cells in the CNS in EAE are thought to be encephalitogenic (Smith and Waksman, 1969;Sedgwick et al, 1987) we cannot exclude the possibility that low dose CsA is blocking apoptosis of encephalitogenic T cells in the CNS. Low dose CsA could also inhibit activation-induced apoptosis of encephalitogenic T cells or their precursors in the thymus.…”

“…IL-2R expression occurs early and transiently after T cell activation (Smith, 1988). The IL-2R population may include the encephalitogenic T cells (Sedgwick et al, 1987).…”