The Kinetics of Cytokine mRNA Expression in the Retina during Experimental Autoimmune Uveoretinitis

Barton, Keith; McLauchlan, M; Calder, Virginia L.; Lightman, Susan

doi:10.1006/cimm.1995.1152

Cited by 40 publications

(19 citation statements)

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“…Cells were washed twice in PBS-0.2% BSA and viable counts were determined on the basis of trypan blue exclusion. No density separation of cells was performed as this was not found to enrich the lymphocyte fraction in accordance with previous reports [26]. Mouse mAb specific for rat cell surface markers were MRC OX1 (anti-CD45), MRC OX6 (anti-MHC classII; I-A), MRC OX39 (anti-CD25 -IL-2R-a chain), MRC OX40 (activated CD4' T cells -member of the TNFRRVGFR family), W3/25 (anti-CD4) and R73 (anti-aPTCR).…”

Section: Retinal Leukocyte Preparation Mab and Flow Cytometrysupporting

confidence: 66%

Inhibition of tumor necrosis factor activity minimizes target organ damage in experimental autoimmune uveoretinitis despite quantitatively normal activated T cell traffic to the retina

et al. 1996

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Recent studies demonstrated that administration of a p55-tumor necrosis factor (TNF) receptor IgG-fusion protein (TNFR-IgG) prevented the clinical onset of experimental autoimmune encephalomyelitis but did not alter the number or tissue distribution of autoantigen-specific CD4+ effector T cells which trafficked into the central nervous system. To determine whether specific target tissues of autoimmune damage remain intact after TNFR-IgG treatment despite the presence of inflammatory cells within the tissues, we examined rats with experimental autoimmune uveoretinitis (EAU), as in this model, the main target of autoreactive CD4+ T cells, the retinal rod outer segments (ROS), can be examined readily by light microscopy. As judged by direct ophthalmoscopy, the onset of inflammation in the anterior chamber of the eye in EAU following administration of TNFR-IgG was delayed by 6 days compared to untreated controls, but the magnitude of the response was only slightly less than controls. Histological examination of the retinae and direct assessment of retinal inflammation revealed a disproportionate sparing of ROS in the TNFR-IgG-treated animals despite a level of retinal inflammation not substantially less than controls in which ROS damage was marked. Analysis of retinal leukocytes by immunofluorescence microscopy and flow cytometry indicated that approximately equal numbers of CD4+ alpha beta TCR+ lymphocytes were present in treated and control retinae, more than 30% of CD4+ cells in both experimental groups expressed the CD25 or MRC OX40 activation markers and most cells, which would include the CD4+ T lymphocytes, were activated as evidenced by MHC class II expression. Fewer activated macrophages and granulocytes were present in the treated retinae, possibly reflecting the lower level of tissue damage and subsequent accumulation of these inflammatory cells. The results demonstrate directly that a tissue specifically targeted for autoimmune destruction can be protected despite the influx of fully activated CD4+ T cells.

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Section: Retinal Leukocyte Preparation Mab and Flow Cytometrysupporting

confidence: 66%

Inhibition of tumor necrosis factor activity minimizes target organ damage in experimental autoimmune uveoretinitis despite quantitatively normal activated T cell traffic to the retina

et al. 1996

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“…If membranes were not to be used the same day, they were baked at 80°C and then stored between 2 sheets of filter paper in a sealed plastic bag at room temperature. To identify the RT-PCR products bound to the membranes, we used the following probe sequences, which are specific for rat cytokines (Barton et al, 1995) and which were synthesized by Gibco BRL Life Technologies:…”

Section: Identification Of Productsmentioning

confidence: 99%

Cytokine expression by inflammatory cells obtained from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis induced by inoculation with myelin basic protein and adjuvants

McCombe

Nickson

Pender

1998

Journal of Neuroimmunology

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Inflammatory cells were obtained from the spinal cords of rats with acute experimental autoimmune encephalomyelitis EAE induced by inoculation with myelin basic protein MBP and adjuvants. Reverse transcriptase-polymerase chain reaction RT-PCR was used to investigate the expression of mRNA for interleukin-2 IL-2 , IL-4, IL-10 and interferon-γ (IFN-γ) by cells from groups of rats studied 10-21 days after inoculation. On all days of study, the inflammatory cells, which were predominantly lymphocytes, expressed mRNA for IL-2, IL-4, IL-10 and IFN-γ. In the mRNA from normal rat spinal cord tissue, there was little expression of cytokine mRNA. Cells from a short-term MBP-reactive T cell line expressed all the cytokines. Densitometry was used to measure the products of PCR, to assess the expression of each cytokine relative to that of β-actin. IL-2 mRNA was expressed throughout the course of disease and reached a peak on day 18, during late clinical recovery. IFN-γ was expressed throughout the course of the disease and was also high during late recovery. IL-4 mRNA was present in the spinal cord throughout the course of the disease, with a slight rise during late recovery. Relative expression of IL-10 rose to a peak on days 17-19, during late recovery from clinical disease. This study indicates that IL-2, IL-4, IL-10 and IFN-γ are expressed by inflammatory cells in the spinal cord in EAE, with the relative expression of all cytokines being high during late clinical recovery.

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“…In a previous report, IL-10 mRNA levels increased more slowly, reaching their maximum at later stages of the disease [22]. Kennedy et al [23] reported a modest increase in IL-10 mRNA levels during the acute phase of experimental autoimmune encephalomyelitis in the spinal cord samples of SJL/J mice whereas it became upregulated and remained elevated throughout the recovery stage.…”

Section: Discussionmentioning

confidence: 93%

“…A previous study has shown that TNF-·, IL-6, IFN-Á and IL-1 are expressed as immunological and inflammatory responses in rat renal allografts, experimental autoimmune uveoretinitis (EAU) and endotoxin-induced uveitis (EIU) [19][20][21][22][23][24]. We showed that the TNF-· and IL-1· mRNAs detected before inflammatory response became gradually upregulated in the iris and ciliary body during EMIU (fig.…”

Section: Discussionmentioning

confidence: 99%

The Expression of Multiple Cytokines and Inducible Nitric Oxide Synthase in Experimental Melanin-Protein-Induced Uveitis

Kim

Yoon²,

Joo³

2001

Ophthalmic Res

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We investigated the kinetics of multiple cytokines and inducible nitric oxide synthase (iNOS) in experimental uveitis induced by bovine melanin protein (BMP) for the proper treatment of uveitis. Experimental uveitis was induced in male Lewis rats by injection of BMP. The levels of various inflammatory cytokines and iNOS mRNAs were semiquantified by the reverse-transcriptase reaction followed by PCR. The uveitis was started to develop at approximately day 14 and peaked around 21 days after immunization. The signs of uveitis disappeared by 4 weeks after immunization. When the inflammation was severest, TNF-α, IL-1α, IL-10, IFN-γ and iNOS mRNA increased to their peak, which varied with the degree of induction and different time course. We concluded that both cytokines and iNOS might modulate the inflammation at different states of experimental melanin-protein-induced uveitis. Their combination will be necessary for an effective treatment of inflammation.

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The Kinetics of Cytokine mRNA Expression in the Retina during Experimental Autoimmune Uveoretinitis

Cited by 40 publications

References 0 publications

Inhibition of tumor necrosis factor activity minimizes target organ damage in experimental autoimmune uveoretinitis despite quantitatively normal activated T cell traffic to the retina

Inhibition of tumor necrosis factor activity minimizes target organ damage in experimental autoimmune uveoretinitis despite quantitatively normal activated T cell traffic to the retina

Cytokine expression by inflammatory cells obtained from the spinal cords of Lewis rats with experimental autoimmune encephalomyelitis induced by inoculation with myelin basic protein and adjuvants

The Expression of Multiple Cytokines and Inducible Nitric Oxide Synthase in Experimental Melanin-Protein-Induced Uveitis

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