scholarly journals Schistosomiasis Decreases Central Nervous System Inflammation and Alters the Progression of Experimental Autoimmune Encephalomyelitis

2003 ◽  
Vol 71 (9) ◽  
pp. 4996-5004 ◽  
Author(s):  
Anne Camille La Flamme ◽  
Kate Ruddenklau ◽  
B. Thomas Bäckström
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Autoimmune Encephalomyelitis ◽  
Th2 Response ◽  
Cns Inflammation ◽  
Necrosis Factor Alpha ◽  
Ifn Γ ◽  
Experimental Autoimmune

ABSTRACT A preestablished infection with the parasitic helminth, Schistosoma mansoni, significantly reduced the incidence and delayed the onset of experimental autoimmune encephalomyelitis (EAE) in C57BL/6J mice immunized with myelin oligodendrocyte glycoprotein (MOG)35-55 peptide. The altered disease progression was not solely due to the induction of a strong Th2 response, since intraperitoneal injection of schistosome eggs did not affect disease development. MOG-specific gamma interferon (IFN-γ), nitric oxide, and tumor necrosis factor alpha production by splenocytes was significantly reduced in schistosome-infected mice compared to uninfected mice. However, similar levels of interleukin-10 (IL-10) were produced in an antigen-specific manner, suggesting that the induction of antigen-specific responses was not inhibited. Analysis of in vivo cytokine production by real-time PCR indicated that IL-12p40, but not IFN-γ, transcript levels were dramatically reduced in the spinal cords of schistosome-infected, MOG-immunized mice. Furthermore, analysis of the cellular composition of the spinal cords and brains revealed that a preestablished infection with S. mansoni decreased central nervous system (CNS) inflammation, particularly of macrophages and CD4 T cells. These results suggest that schistosomiasis may negatively regulate the onset of EAE by downregulating the production of proinflammatory cytokines and altering CNS inflammation.

scholarly journals Failure to Suppress the Expansion of the Activated Cd4 T Cell Population in Interferon γ–Deficient Mice Leads to Exacerbation of Experimental Autoimmune Encephalomyelitis

2000 ◽  
Vol 192 (1) ◽  
pp. 123-128 ◽  
Author(s):  
Cong-Qiu Chu ◽  
Susan Wittmer ◽  
Dyana K. Dalton
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Cd4 T Cells ◽  
Wild Type ◽  
Autoimmune Encephalomyelitis ◽  
Ifn Γ ◽  
Experimental Autoimmune

Mice deficient in interferon (IFN)-γ or IFN-γ receptor develop progressive and fatal experimental autoimmune encephalomyelitis (EAE). We demonstrate that CD4 T cells lacking IFN-γ production were required to passively transfer EAE, indicating that they were disease-mediating cells in IFN-γ knockout (KO) mice. IFN-γ KO mice accumulated 10–16-fold more activated CD4 T cells (CD4+CD44hi) than wild-type mice in the central nervous system during EAE. CD4+CD44hi T cells in the spleen and central nervous system of IFN-γ KO mice during EAE showed markedly increased in vivo proliferation and significantly decreased ex vivo apoptosis compared with those of wild-type mice. IFN-γ KO CD4+CD44hi T cells proliferated extensively to antigen restimulation in vitro and accumulated larger numbers of live CD4+ CD44hi T cells. IFN-γ completely suppressed proliferation and significantly induced apoptosis of CD4+CD44hi T cells responding to antigen and hence inhibited accumulation of live, activated CD4 T cells. We thus present novel in vivo and in vitro evidence that IFN-γ may limit the extent of EAE by suppressing expansion of activated CD4 T cells.

scholarly journals The Clinical Course of Experimental Autoimmune Encephalomyelitis and Inflammation Is Controlled by the Expression of Cd40 within the Central Nervous System

2001 ◽  
Vol 193 (8) ◽  
pp. 967-974 ◽  
Author(s):  
Burkhard Becher ◽  
Brigit G. Durell ◽  
Amy V. Miga ◽  
William F. Hickey ◽  
Randolph J. Noelle
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Inflammatory Cell ◽  
Chimeric Mice ◽  
Autoimmune Encephalomyelitis ◽  
Cns Inflammation ◽  
Organ Specific ◽  
The Central Nervous System ◽  
Experimental Autoimmune

Although it is clear that the function of CD40 on peripheral hematopoietic cells is pivotal to the development of autoimmunity, the function of CD40 in autoimmune disease outside this compartment is unresolved. In a model of experimental autoimmune encephalomyelitis (EAE), evidence is presented that CD40–CD154 interactions within the central nervous system (CNS) are critical determinants of disease development and progression. Using bone marrow (BM) chimeric mice, the data suggest that the lack of expression of CD40 by CNS-resident cells diminishes the intensity and duration of myelin oligodendrocyte glycoprotein (MOG)-induced EAE and also reduces the degree of inflammatory cell infiltrates into the CNS. Although CNS inflammation is compromised in the CD40+/+→CD40−/− BM chimeric mice, the restricted CD40 expression had no impact on peripheral T cell priming or recall responses. Analysis of RNA expression levels within the CNS demonstrated that encephalitogenic T cells, which entered a CNS environment in which CD40 was absent from parenchymal microglia, could not elicit the expression of chemokines within the CNS. These data provide evidence that CD40 functions outside of the systemic immune compartment to amplify organ-specific autoimmunity.

scholarly journals CD8+ T cells specific for cryptic apoptosis-associated epitopes exacerbate experimental autoimmune encephalomyelitis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Neda Feizi ◽  
Chiara Focaccetti ◽  
Ilenia Pacella ◽  
Gloria Tucci ◽  
Alessandra Rossi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Disease Severity ◽  
Effector Memory ◽  
Autoimmune Encephalomyelitis ◽  
The Central Nervous System ◽  
Experimental Autoimmune

AbstractThe autoimmune immunopathology occurring in multiple sclerosis (MS) is sustained by myelin-specific and -nonspecific CD8+ T cells. We have previously shown that, in MS, activated T cells undergoing apoptosis induce a CD8+ T cell response directed against antigens that are unveiled during the apoptotic process, namely caspase-cleaved structural proteins such as non-muscle myosin and vimentin. Here, we have explored in vivo the development and the function of the immune responses to cryptic apoptosis-associated epitopes (AEs) in a well-established mouse model of MS, experimental autoimmune encephalomyelitis (EAE), through a combination of immunization approaches, multiparametric flow cytometry, and functional assays. First, we confirmed that this model recapitulated the main findings observed in MS patients, namely that apoptotic T cells and effector/memory AE-specific CD8+ T cells accumulate in the central nervous system of mice with EAE, positively correlating with disease severity. Interestingly, we found that AE-specific CD8+ T cells were present also in the lymphoid organs of unprimed mice, proliferated under peptide stimulation in vitro, but failed to respond to peptide immunization in vivo, suggesting a physiological control of this response. However, when mice were immunized with AEs along with EAE induction, AE-specific CD8+ T cells with an effector/memory phenotype accumulated in the central nervous system, and the disease severity was exacerbated. In conclusion, we demonstrate that AE-specific autoimmunity may contribute to immunopathology in neuroinflammation.

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