TH2 activated cells prevent experimental autoimmune uveoretinitis, a TH1‐dependent autoimmune disease

Abstract

Mercuric chloride (HgCl2) injections protect (Lewis x Brown-Norway) F1 (F1) rats against experimental autoimmune uveoretinitis (EAU) induced by immunization with the retinal S antigen (S-Ag); in contrast HgCl2-injected F1 rats develop EAU following transfer of lymph node (LN) cells from rats immunized with S-Ag alone. In the present study we demonstrate that the ability of LN cells from rats protected against EAU to transfer the disease into naive F1 rats was considerably reduced. These LN cells neither produced interleukin (IL)-2 nor (interferon (IFN)-gamma but exhibited mRNA for IL-4. In contrast, LN cells from diseased rats easily transferred EAU into naive F1 rats, produced significant IL-2 and IFN-gamma levels but barely exhibited mRNA for IL-4. Furthermore protected rats predominantly produced IgG1 anti-S-Ag antibodies, while diseased rats produced IgG2b anti-S-Ag antibodies and the increase in expression of MHC class II molecules on B cells was higher in protected rats than in diseased rats. These data suggest that (1) to exert a protective effect, HgCl2 must act at an early stage of differentiation of precursors of S-Ag specific T cells, and (2) this effect is related to the preferential activation of TH2 cells to the detriment of uveitogenic TH1 cells. Finally, these results indicate that activation of TH2 cells protect from a TH1-dependent autoimmune disease.

Prevention of experimental autoimmune uveoretinitis by blockade of osteopontin with small interfering RNA

“…A massive inflammatory infiltration composed primarily of mononuclear cells causes a rapid and irreversible destruction of photoreceptor cells (Jiang et al 1999;Silver et al 1999;Caspi 2003;Amadi-Obi et al 2007;Luger et al 2008). It has been demonstrated that the augmentation of the Th2 response and T regulatory cytokine production and down-regulation of the Th1 response can mitigate inflammation and protect against the development of EAU (Saoudi et al 1993;Kezuka et al 1996;Caspi 2002). …”

Recruitment of IFN-γ-Producing (Th1-Like) Cells into the Inflamed Retina In Vivo Is Preferentially Regulated by P-Selectin Glycoprotein Ligand 1:P/E-Selectin Interactions

“…EAU is also a self-limited autoimmune disease. Resolution of the inflammation during the late stage of disease has been suggested to be due to the Th2 cell response (23,24), with Th2-type cytokines such as IL-4, TGF-␤ (25,26), and IL- 10 (5, 27) shown to suppress EAU despite the fact that adoptive transfer of Th2 cells failed to protect against Th1 cell-induced EAU (8).…”

Augmentation of natural immunity to a pro-inflammatory cytokine (TNF-alpha) by targeted DNA vaccine confers long-lasting resistance to experimental autoimmune encephalomyelitis

“…22,23,[30][31][32][68][69][70][71][72] The current study demonstrates, for the first time, the appearance of 'natural' antiself antibodies to a key pro-inflammatory cytokine, TNF-␣, during the development of a T cell-mediated autoimmune disease of the CNS. These antibodies developed in rats immunized with p68-86/CFA and not with the CFA alone (Figure 3), even though both groups exhibited an extensive local inflammatory process at the site of CFA immunization.…”

“…This type of control has been termed peripheral tolerance. T cell anergy, 69 active suppression, 31,[68][69][70] T cell deletion 93,94 and generation of anti-idiotypic immunity 95 have been described as key mechanisms that contribute to the maintenance of peripheral tolerance. The current study suggests, for the first time, that self-specific T and B cells, capable of mounting self-specific immunity against pro-inflammatory mediators, escape central tolerance to provide the immune system with a powerful tool with which it keeps its dangerous anti-self activity under control and thus maintains tolerance to self in the periphery.…”

“…[12][13][14][15][16][17][18][19][20][21] Th1 cells selected in response to various autoantigens transfer T cell-mediated autoimmune diseases, whereas IL-4-secreting Th2 cells, selected in response to these same antigens, either inhibit or exert no profound effect on the inflammatory process. 16,[22][23][24][25][26][27][28][29][30][31][32][33][34] High levels of IFN-␥ and low levels of IL-4 positively select for Th1 cells, whereas low levels of IFN-␥ together with high levels of IL-4 mediate Th2 selection. [12][13][14][15][16][17] In a recent study, we isolated mRNA encoding interferon gamma-inducing factor (IGIF, IL-18) from the EAE brain, generated neutralizing antibodies against its gene product and explored the critical role of IGIF in T cell selection and regulation of disease.…”