Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This article is to study the relationship between T-lymphocyte subpopulation and soluble interleukin-2 receptor (SIL-2R) in recurrent herpetic keratitis. We detected the T-lymphocyte subpopulation of peripheral blood and soluble interleukin-2 receptor(SIL-2R) in 30 cases of recurrent herpetic keratitis, 25 cases of healthy people were set as contrast. The results showed that there were obvious decrease and of CD3, CD4/CD8, and magnificent elevation of soluble interleukin-2 receptor(SIL-2R) in sera of recurrent herpetic keratitis cases when compared with the contrasts, we hold that the lower immune function in recurrent herpetic keratitis cases may attribute to the high level of soluble interleukin-2 receptor (SIL-2R) in the serum. The discovery can provide foundation for immunotherapy.
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PMID:[Relationship between T-lymphocyte subpopulation and soluble interleukin-2 receptor (SIL-2R) in recurrent herpetic keratitis]. 1251 77

Herpetic stromal keratitis (HSK), resulting from ocular infection with herpes simplex virus (HSV), is thought to represent a T cell mediated immunopathologic lesion. Antigens recognized by the inflammatory T cells remain unresolved and non-TCR mediated activation of T cells (bystander activation) is considered as also involved. This report documents further evidence for the bystander activation mechanisms using three T cell transgenic RAG-/- mouse strains. Accordingly HSK occurred in PCC RAG-/-, P14 RAG-/-, and OT-1 RAG-/- mice. In none of the models could HSV specific T cell reactivity be demonstrated and animals were unprotected from lesion development by immunization prior to HSV ocular infection. The results support the role of bystander activation as a mechanism of T cell mediated immunopathology and show that CD8(+) as well as CD4(+) T cells can participate in HSK lesion development.
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PMID:Herpetic stromal keratitis in the absence of viral antigen recognition. 1257 29

Herpetic stromal keratitis (HSK) is a T helper type 1 cell-mediated inflammatory disease triggered by herpes simplex virus (HSV) infection of the cornea. In contrast to animal models of HSK, little is known about the role of T cells in human HSK. The phenotypes and repertoires of HSV-specific T cells recovered from the corneas of 12 patients with HSK were determined by flow cytometry. Cornea-derived T cell lines (TCLs) from 10 of the 12 patients contained high numbers of HSV-specific T cells. HSV reactivity was HSV type common and involved relatively more CD8(+) than CD4(+) T cells. The majority of the TCLs showed restricted T cell receptor beta-chain variable region protein (TCRBV) use. T cells expressing 1 or 2 TCRBVs dominated the HSV-1 reactivity in 3 of 5 TCLs analyzed. The data demonstrate that both CD4(+) and CD8(+) T cells may be involved in the HSV-specific T cell response in the corneas of patients with HSK and suggest that restricted TCRBV use by cornea-residing HSV-specific T cells occurs.
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PMID:Restricted T cell receptor beta-chain variable region protein use by cornea-derived CD4+ and CD8+ herpes simplex virus-specific T cells in patients with herpetic stromal keratitis. 1259 71

The role of immunologic factors in the development of ophthalmic pathologies in persons infected by hepatitis B virus (HBV) affecting the liver or in asymptomatic virus carriers (a total of 285 persons, 328 eyes) was studied. The deficit of CD3 and CD4 cells, gammopathy, increased levels of circulating immune complexes and of TNF-alpha in the serum; the deficit of IgA and an enhanced secretion of IgG in the lachrymal fluid; as well as a weakened ability of the local and systematic production of IFN-alpha were typical for a majority of patients. The most profound changes were detected in cases of uveitis; apart from the above mentioned, an increase of the CD4/CD8 index as well as of organ-specific and inter-organ immunization was found. The cases of keratitis (92% of the stromal type) were distinguished through a hypersecretion of TNF-alpha both in the serum and in the lachrymal fluid. Complicated cataracts were observed mainly in convalescents or in asymptomatic virus carriers; immune disorders were less seldom encountered in this category, as compared to the cases of eye inflammations, and basically they were local. The obtained data were considered in treatment. Imunofan, when added to the traditional therapy (symptomatic and corticosteroid one), activated the local and systematic antiviral immunity, suppressed the production of pro-viral cytokines and reduced the autoimmune reactions. As a result of this, the treatment time, the frequency rate of relapses as well as the number of anti-inflammatory and postoperative (in cataracts) complications decreased. The study results are indicative of that the immunopathological reactions, which are typical of HBV patients, can be detected at the ocular level and they can provoke ophthalmic pathologies. The nature, severity and relation between the local and systematic immune disorders predetermine, to a considerable extent, the development of an eye disease and its severity. The treatment (and prophylaxis) of HBV-associated ophthalmic pathologies require an obligatory usage of immunity-correcting means and clinical-and-immunological monitoring.
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PMID:[The role of immunopathological reactions in the development of eye diseases in persons infected by hepatitis B virus and the efficiency of immuno-correcting therapy]. 1280 Apr 83

Herpes stromal keratitis (HSK) is the leading infectious cause of blindness in the United States and is a consequence of events following HSV-1 infection of the eye. The pathology of the disease is currently thought to be caused by a destructive, CD4(+) T helper 1 (Th1) type inflammatory immune response within the cornea rather than a cytopathic response elicited by the virus. A large percentage of people can become infected with HSV-1 as children whereas some studies have concluded that many others do not become infected with HSV-1 until much later in life. In this paper we investigate the role of increasing age on ocular HSV-1 infection. Following an ocular infection of mice with HSV-1 we observed greater pathology in the cornea during both early and late time-points in adult mice when compared to young animals. No significant differences in viral titers were observed in either the eyes or trigeminal ganglia from infected mice, regardless of age, suggesting that increased viral load may not be responsible for the ocular pathology in the adult mice. We hypothesize that age-related changes in the immune response may predispose adult animals to HSK disease.
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PMID:Influence of increased age on the development of herpes stromal keratitis. 1458 Aug 74

CD4(+)CD25(+) regulatory T cells (T(reg)) can inhibit a variety of autoimmune and inflammatory diseases, but their involvement in regulating virus-induced immunopathology is not known. We have evaluated the role of T(reg) in viral immunopathological lesion stromal keratitis. This frequent cause of human blindness results from a T cell-mediated immunoinflammatory response to HSV in the corneal stroma. The results show that lesions were significantly more severe if mice were depleted of T(reg) before infection. The T(reg) was also shown to modulate lesion expression induced by adoptive transfer of pathogenic CD4(+) T cells in infected SCID recipients. The mechanism of T(reg) control of stromal keratitis involved suppressed antiviral immunity and impaired expression of the molecule required for T cell migration to lesion sites. Interestingly, T(reg) isolated from ocular lesions in nondepleted mice showed in vitro inhibitory effects involving IL-10, but were not very effective in established lesions. Our results decipher the in vivo role of T(reg) in a virus-induced immunopathology and imply that manipulation of regulatory cell function represents a useful approach to control viral-induced immunoinflammatory disease.
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PMID:CD4+CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions. 1503 24

The ability of autoreactive T cells to provoke autoimmune disease is well documented. The finding that immunization with attenuated autoreactive T cells (T cell vaccination, or TCV) can induce T cell-dependent inhibition of autoimmune responses has opened the possibility that regulatory T cells may be harnessed to inhibit autoimmune disease. Progress in the clinical application of TCV, however, has been slow, in part because the underlying mechanism has remained clouded in uncertainty. We have investigated the molecular basis of TCV-induced disease resistance in two murine models of autoimmunity: herpes simplex virus-1 (KOS strain)-induced herpes stromal keratitis and murine autoimmune diabetes in non-obese diabetic (NOD) mice. We find that the therapeutic effects of TCV depend on activation of suppressive CD8 cells that specifically recognize Qa-1-bound peptides expressed by autoreactive CD4 cells. We clarify the molecular interaction between Qa-1 and self peptides that generates biologically active ligands capable of both inducing suppressive CD8 cells and targeting them to autoreactive CD4 cells. These studies suggest that vaccination with peptide-pulsed cells bearing the human equivalent of murine Qa-1 (HLA-E) may represent a convenient and effective clinical approach to cellular therapy of autoimmune disease.
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PMID:Suppression of autoimmune disease after vaccination with autoreactive T cells that express Qa-1 peptide complexes. 1508 1

The role that T cell subsets play in herpetic stromal keratitis (HSK) has been the subject of intense research efforts. While most studies implicate CD4(+) T cells as the principal cell type mediating primary corneal disease, recent reports using knockout mice have suggested that both CD4(+) and CD8(+) T cell subsets may play integral roles in modulating the disease. Furthermore, recent studies suggest that CD8(+) T cells are directly involved in maintaining virus latency in infected trigeminal ganglia. This work has addressed these discrepancies by infecting the corneas of mice lacking CD4(+) and CD8(+) T cells with herpes simplex virus type 1 (HSV-1) and monitoring both corneal disease and latent infection of trigeminal ganglia. Results indicated that mice lacking CD8(+) T cells had more severe corneal disease than either BALB/c or B6 parental strains. In contrast, mice lacking CD4(+) T cells had a milder disease than parental strains. When mice were evaluated for persistence of infectious virus, only transient differences were observed in periocular tissue and corneas. No significant differences were found in persistence of virus in trigeminal ganglia or virus reactivation from explanted ganglia. These data support the following conclusions. CD4(+) T cells are not required for resistance to infection with HSV-1 and probably mediate HSK. Mice lacking CD8(+) T cells do not display differences in viral loads or reactivation and thus CD8(+) T cells are not absolutely required to maintain latency. Finally, CD8(+) T cells probably play a protective role by regulating the immunopathological response that mediates HSK.
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PMID:CD8(+) T cells control corneal disease following ocular infection with herpes simplex virus type 1. 1521 91

Approximately 7 days after HSV-1 corneal infection, BALB/c mice develop tissue-destructive inflammation in the cornea termed herpes stromal keratitis (HSK), as well as periocular skin lesions that are characterized by vesicles, edema, and fur loss. CD4(+) T cells and Th1 cytokines contribute to both the immunopathology in the cornea and the eradication of viral replication in the skin. We demonstrate that disruption of CD40/CD154 signaling does not impact the initial expansion of CD4(+) T cells in the draining lymph nodes, but dramatically reduces the persistence and Th1 polarization of these cells. Despite the reduced Th1 response, CD154(-/-) mice developed HSK and periocular skin disease with similar kinetics and severity (as assessed by clinical examination) as wild-type (WT) mice. However, when the composition of the inflammatory infiltrate was examined by flow cytometric analysis, CD154(-/-) mice exhibited significantly fewer CD4(+) and CD8(+) T cells and neutrophils than WT mice at the peak of HSK. Moreover, CD4(+) T cells from infected corneas of CD154(-/-) mice produced significantly less IFN-gamma than those of WT mice when stimulated with viral Ags in vitro. The IFN-gamma production of cells from infected corneas of WT mice was not affected by addition of anti-CD154 mAb to the stimulation cultures. This suggests that CD154 signaling is required at the inductive phase, but not at the effector phase, of the Th1 response within the infected cornea. We conclude that local disruption of CD40/CD154 signaling is not likely to be a useful therapy for HSK.
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PMID:CD154 signaling regulates the Th1 response to herpes simplex virus-1 and inflammation in infected corneas. 1524 Jul 15

Fumaric acid derivates have been shown to stimulate T helper-2-cytokines (interleukin (IL)-4, -5) without affecting the T-helper-1-cytokine (IL-2, interferon (IFN)-gamma)-response. Herein, the influence of systemic treatment with the fumaric acid derivate dimethylfumarate (DMF) on the secretion of T helper-cytokines and the development of HSV-1 stromal keratitis (HSK) was studied in mice. The corneas from BALB/c mice were infected with 10(5) PFU of HSV-1 (KOS strain). While one group of mice was treated intraperitoneally with PBS, another group of mice received DMF at 15 mg/kg of body weight. Expression of IL-2, -4, -10 and IFN-gamma was analysed in HSV-1 activated lymphocytes by ELISA. The severity of epithelial and stromal herpetic keratitis was investigated clinically. Corneas were studied for the inflammatory cell infiltration, and the CD3-, CD4- and CD8-positive cells were analysed by immunohistochemistry. The IL-2, -4, 10 and IFN-gamma content was measured in the corneas. Virus replication in the eyes was analysed by a plaque-assay. The DTH-response, the HSV-specific T cell proliferation and the serum neutralizing antibody-titres were investigated. DMF increased IL-4 and IL-10, but not IL-2 and IFN-gamma, secretion in activated lymphocytes from the spleen. Incidence and severity of stromal HSV-1 keratitis was reduced in the DMF group (P < 0.01). In the corneas from DMF-treated mice, the numbers of CD3+ and CD4+ cells were decreased and IL-4 was increased. Severity of epithelial disease and the virus-clearance from the eyes did not differ between the PBS and DMF group of mice. DTH, HSV-specific T cell proliferation and the neutralizing antibody-titres were not impaired. DMF increased the T helper-2-cytokine secretion in activated lymphocytes. After corneal HSV-1 infection, corneas from DMF treated mice had increased IL-4 content. This is associated with an improvement of herpetic stromal keratitis and reduced corneal T cell infiltration. DMF did not impair the systemic antiviral response.
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PMID:Improvement of herpetic stromal keratitis with fumaric acid derivate is associated with systemic induction of T helper 2 cytokines. 1617 74


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