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)

The pathogenesis of peripheral corneal lesions of immune aetiology, like Mooren's ulcer and catarrhal infiltrates, has been related to the formation or deposition of immune compkexes. The present investigation was undertaken to study the mechanisms involved in the elimination of immune precipitates from the cornea. Immune precipitates were induced by injecting human serum albumin (HSA) and rabbit anti-HSA serum into opposite sites of the rat corneal stroma. This resulted in a line-shaped opacity in the stroma, which remained visible by slit-lamp for 7 days, and disappeared without clinical signs of keratitis and uveitis. At the ultrastructural level, the immune precipitates were clearly visible. Keratocytes in the vicinity of the immune precipitates appeared activated, as suggested by their less flattened appearance and well-developed rough endoplasmic reticulum. The arrangement of the collagen fibrils was not affected. Cells with a macrophage-like morphology were also present and contained electron-dense material, closely resembling the precipitate, suggesting phagocytosis. Separate corneas were injected with latex beads, which is known to induce migration of Langerhans cells into the cornea. Immunohistochemical analysis revealed that both latex beads and immune precipitates induced migration of macrophages (ED1+) into the rat corneal stroma. However, differences were observed with regard to the expression of MHC class II antigens by these ED1+ cells and the presence of complement deposits in the corneal stroma. ED1+ cells in corneas injected with latex beads were all MHC class II positive (OX4+), whereas most of the ED1+ cells at the site of the immune precipitates were negative (OX4-).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elimination of immune precipitates from the rat corneal stroma: a histological study. 193 83

The corneal buttons obtained from 4 patients with active epithelial and stromal herpetic keratitis were studied with routine microscopy and immunohistochemistry. We used an immunoperoxidase technique with monoclonal antibodies directed against Langerhans cells, lymphocyte subsets, MHC products and immunoglobulins A, G, M and D. The epithelium and stroma contained an inflammatory infiltrate composed of polymorpho-nuclear leukocytes, dendritic cells, B-lymphocytes and T-lymphocytes (helper/inducer and suppressor/cytotoxic subsets). The epithelial cells of all the corneal buttons expressed MHC class II antigens. IgM was bound to the membrane of the epithelial cells in 3 specimens. HSV antigenic material was localized in the epithelial cells and in the stromal keratocytes by a direct immunofluorescence technique. Our data suggest that cell-mediated as well as antibody-mediated immune responses are involved, with a possible role for an autoimmune mechanism in the pathogenesis of this condition.
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PMID:Expression of MHC class II antigens and immunoglobulin M by the corneal epithelial cells in herpetic keratitis. 214 84

BALB/c inbred Igh-1-disparate mice exhibit different susceptibility to the development of HSV-1 stromal keratitis (HSK), which may be due to the differential immune regulation. CD4+ T lymphocytes may be critical for the disease induction. A T-cell line (CD4+, T-cell receptor V beta 8+, interleukin-4+) specific for the N-terminal amino acids 5-23 of glycoprotein D from HSV-1 [gD(5-23)] was established from HSK susceptible C.AL-20 mice. HSK-resistant C.B-17 mice, and HSK-susceptible BALB/c mice were injected intraperitoneally with cells (5 x 10(5)/mouse) alone or combined with HSV-1 corneal inoculation (10(5) PFU, KOS strain). Control groups were injected with HSV-antigen-unrelated cells (PPD specific), or were only HSV-1 infected. Migration of the adoptively transferred gD(5-23) Th2 cells was analyzed by histology, by immunohistochemistry and by cell membrane labelling (PKH26). The transfer of gD(5-23) cells accelerated the disease onset (day 2, compared to day 7 without cells). The transfer of gD(5-23) cells increased the incidence of HSK (BALB/c 100%, C.B-17 20%) compared to mice that were only infected with HSV-1 (BALB/c 75%, C.B-17 0%). Keratitis was more severe in mice injected with gD(5-23) cells. In contrast, the transfer of PPD-specific cells did not influence the disease patterns. Mice injected with gD(5-23) cells and not inoculated with HSV-1 did not develop keratitis. The results suggest that CD4+ MHC class II, V beta 8+, IL-4 expressing T-cells (T helper 2) may be important for the induction of HSK.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Glycoprotein D (5-23) specific Th2-T-cell line induces HSV-1 keratitis]. 754 33

Peptide analogues containing reversed peptide bonds between each residue along the peptide sequence (retro-inverso modification) have been analyzed for their antigenic and in vivo immunogenic properties in the MHC II and Th cell response context. Two antigenic peptides were selected for this study, namely peptide 103-115 of poliovirus VP1, which is involved in the production of Abs that neutralize the infectivity of the virus, and peptide 435-446 from the third constant region of mouse heavy chain IgG2a allopeptide gamma 2ab, which mimics a corneal Ag implicated in autoimmune keratitis. In a competition assay performed in vitro using reference hybridomas of known MHC class II restriction, both retro-inverso analogues bound (although more weakly in our test) to I-Ad and/or I-Ed class II molecules. However, in both cases, this lower affinity was apparently largely compensated in vivo, as a T cell response (with IL-2 secretion), equivalent to that obtained with the wild-type peptides, was observed following immunization of BALB/c mice with the retro-inverso analogues. Moreover, these T cells proliferated and produced IL-2 in response to the cognate peptides. It is concluded that the T cell receptors of T cells primed in vivo with the retro-inverso analogues readily cross-react with parent and retro-inverso analogue-MHC complexes. The approach of using pseudopeptides containing changes involving the backbone, and not the orientation of side chains, may thus be promising to design potent immunogens for class II-restricted T cells.
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PMID:In vivo T helper cell response to retro-inverso peptidomimetics. 931 21

The IgG2a(b) heavy chain allopeptide determinant gamma2a(b) 436-451 (Kabat numbering) presented by the major histocompatibility complex (MHC) class II molecule I-Ad is recognized by T cells which cross-react with a corneal self antigen and with the UL6 protein of the herpes simplex virus which induce autoimmune keratitis, and is the target of Th1 clones that suppress IgG2a(b) production in vivo. In the gamma2a(b) peptide/l-Ad complex, tyrosine438 is the first primary anchor (P1) and residues 440-445 encompass the T cell receptor contact residues. Amino-terminal elongation of gamma2a(b) 437-451 by a single residue (P-2) augmented the I-Ad binding capacity 10-fold and the antigenicity 55-195-fold. This was a function of the peptide main chain, since non-conservative substitutions were accepted. The gamma2a(b) peptide also bound HLA-DR1, and amino-terminal extension by a single aromatic amino acid at P-3 augmented binding 15-fold. The interaction between HLA-DR1 and P-3 specifically required an aromatic peptide side chain, and computer simulations indicated that the aromatic ring at P-3 engaged conserved HLA-DR1 phenylalanine residues at the edge of the peptide binding groove. Thus, these data demonstrate that residues amino terminal to P1 may substantially increase peptide affinity for MHC class II by main chain-dependent as well as side chain-dependent interactions, and imply that the HLA-DR1 motif should be extended to include an aromatic amino acid at P-3.
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PMID:N-terminal elongation of a peptide determinant beyond the first primary anchor improves binding to H-2 I-Ad and HLA-DR1 by backbone-dependent and aromatic side chain-dependent interactions, respectively. 993

The murine MHC class II variant I-Ad confers susceptibility to herpes simplex virus (HSV)-induced keratitis and relative protection against type 1 diabetes mellitus. The association to these autoimmune diseases appears to be largely determined by the peptide sidechain specificity of the P9 pocket, which we therefore have analyzed in detail. Assessment of T-cell responses and I-Ad binding capacity of position 446-substituted analogs of an IgG2a allotype b (IgG2a(b)) heavy chain peptide demonstrates that engagement of the P9 pocket is crucial for effective peptide presentation. Sidechain size rather than charge decides the capacity to engage the P9 pocket. Thus, small, uncharged sidechains are accepted, whereas acidic and aromatic amino acids as well as lysine and arginine are disfavored. The specificity of the P9 pocket of I-Ad (serine beta57) is distinct from that of the diabetes-associated I-Ag7 (aspartic acid beta57), supporting the contention that the polymorphism at residue beta57 influences diabetes susceptibility via P9-specific effects on the repertoires of self peptides presented to T cells. Furthermore, the data rationalize the susceptibility to HSV-induced keratitis conferred by the a and the protection conferred by the b allotypes of the IgG2a heavy chain. Keratitogenic T cells, which cross-react with the viral UL6 protein and a corneal antigen, are silenced in IgG2a(b) mice because of antigenic mimicry with gamma2a(b) 435-451. Our finding that the lysine P9 residue of the corresponding gamma2a(a) allopeptide precludes high-affinity binding to I-Ad indicates that the susceptibility of IgG2a(a) mice reflects inefficient thymic presentation of autologous IgG2a and thus failure to purge the T-cell repertoire of the pathogenic clones.
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PMID:The P9 peptide sidechain specificity of I-Ad. 1065 74

Peptide epitopes derived from immunoglobulin variable regions represent tumour-specific antigens on B-cell neoplasms and can be recognized by syngeneic, major histocompatibility complex (MHC) class II-restricted T cells. Immunoglobulin peptide/MHC class II complexes may also be involved in autoimmunity and CD4+ T-cell-mediated B-cell regulation. Thus, the IgG2a(b) H-chain allopeptide gamma2a(b) 435-451 presented on I-Ad mimics the epitope implicated in herpes simplex virus-induced autoimmune stromal keratitis and is the target of T helper 1 (Th1) clones that suppress IgG2a(b) production in vivo. We here report that spleen and thymus cells constitutively present the autologous gamma2a(b) epitope to a gamma2a(b) 435-451/I-A(d) reactive T-cell hybridoma as a function of the animal housing conditions (specific pathogen-free or not) and the serum levels of IgG2a(b). Constitutive presentation in the spleen was predominantly performed by dendritic cells. Whereas spleen cells poorly presented native IgG2a(b) to a gamma2a(b) 435-451/I-A(d) reactive T-cell hybridoma, IgG2a(b) in the form of immune complexes were presented > 200-fold more efficiently owing to internalization via low-affinity FcgammaR on macrophages. The antigenicity could also be improved by homotypic aggregation and by targeting IgG2a(b) to complement receptors on the A20 B-cell lymphoma. Mice without detectable IgG2a(b)-containing immune complexes typically exhibited minimal constitutive presentation. Nevertheless, native IgG2a(b) can sensitize antigen-presenting cells in vivo, as mice that were devoid of immune complexes and carried an IgG2a(b)-producing tumour did present constitutively, even at physiological IgG2a(b) serum levels. Whereas the amounts of IgG released from most B-cell lymphomas may be too low to allow spontaneous priming of tumour-specific MHC class II-restricted T cells, administration of tumour immunoglobulin in aggregated form might improve the efficacy of idiotype vaccination.
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PMID:Native IgG2a(b) is barely antigenic to major histocompatibility complex class II-restricted T cells owing to inefficient internalization by professional antigen-presenting cells. 1079 98

Keratocytes express MHC class I molecules constitutively, and keratocytes stimulated with IFN-gamma express MHC class II molecules. Unstimulated keratocytes constitutively express B7-1 and ICAM-1, as well as low levels of CD40 and 4-1BBL. These findings indicate that keratocytes may deliver both antigen-specific and costimulatory signals to CD4(+) and CD8(+) T cells. To demonstrate that keratocytes expressing B7-1 provide a costimulatory signal to T cells, CD4(+) or CD8(+) mouse T cells were incubated with anti-CD3 mAb and irradiated keratocytes. Enhanced proliferation of both CD4(+) and CD8(+) T cells occurred, and could be inhibited by anti-B7-1 mAb, indicating T cell costimulatory activity by B7-1 on the keratocytes. To demonstrate that keratocytes can deliver an antigen-specific signal, CD4(+) and CD8(+) T cells from herpes-infected mice were incubated with HSV-1-infected, irradiated keratocytes. The resulting T cell proliferation and production of Th1 cytokines (IL-2, IFN-gamma) indicated T cell activation by antigens presented by the infected keratocytes. These results show that keratocytes in the corneal stroma of the mouse can function as antigen-presenting cells and, thus, may play a role in immune-mediated stromal inflammation such as herpetic stromal keratitis.
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PMID:Murine keratocytes function as antigen-presenting cells. 1174 49

Herpetic stromal keratitis (HSK) and blepharoconjunctivitis in humans are thought partly to result from immunopathological responses to herpes simplex virus type 1 (HSV-1). The corneas of NIH mice were inoculated with HSV-1 (strain McKrae) and mice were examined for signs of disease and infection on days 1, 4, 7, 10, 14 and 21. The eyes and eyelids of infected and control mice were processed for immunohistochemistry and double stained for viral antigens and one of the following cell surface markers (Gr-1, F4/80, CD4, CD8, CD45R or MHC class II) or one of the following cytokines (IL-2, IL-4, IL-6, IL-10, IL-12 or IFN-gamma). All infected mice developed signs of HSK by day 4 and blepharitis by day 7 and these both persisted until day 21, when signs of resolution where apparent. Virus was detected during the first week of infection and became undetectable by day 10. Large numbers of Gr-1(+) cells (neutrophils) infiltrated infected corneas and eyelids in areas of viral antigen and CD4(+) T cells increased significantly in number after virus clearance. In both sites, the predominant cytokines were IL-6, IL-10, IL-12 and IFN-gamma, with few IL-2(+) and IL-4(+) cells. These observations suggest that the immune responses in the cornea are similar to those in the eyelids but, overall, the responses are not clearly characterized as either Th1 or Th2. In both sites, the neutrophil is the predominant infiltrating cell type and is a likely source of the cytokines observed and a major effector of the disease process.
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PMID:Primary herpes simplex virus type 1 infection of the eye triggers similar immune responses in the cornea and the skin of the eyelids. 1207 76

Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers CD4(+) T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in CD4(+) T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed CD4(+) T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed CD4(+) T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of CD4(+) T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts CD4(+) T cells into the cornea.
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PMID:MCP-1 derived from stromal keratocyte induces corneal infiltration of CD4+ T cells in herpetic stromal keratitis. 1859 81


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