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)

T lymphocytes are critical in mediating herpes simplex stromal keratitis (HSK). Using immunohistologic methods, we studied the T cell subsets and the T cell receptor variable region (TCR V beta) repertoire of T cells in the eye after corneal infection with HSV (KOS strain). We investigated the possibility that there might be differential V beta preferential usage in HSK resistant and susceptible BALB/c congenic mice that differ only in a small region associated with the Igh-1 gene locus. The inflamed corneas of HSK susceptible C.AL-20 mice were mainly infiltrated by CD4+ cells and by V beta 8 expressing cells. Such T cells were not seen in the corneas of resistant C.B-17 mice. Our results indicate that CD4+V beta 8+ cells are involved in mediating HSV-1 stromal keratitis.
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PMID:CD4+V beta 8+ T cells mediate herpes stromal keratitis. 784 19

Our study examined T cell receptor (TCR) V beta mRNA expression in a murine model of experimental herpes simplex keratitis (HSK). We employed a polymerase chain reaction (PCR) technique to detect TCR V beta mRNA expression in the inoculated eyes of both HSK-susceptible and HSK-resistant mice at different time points after corneal inoculation with herpes simplex virus type 1 (HSV-1), followed by Southern blotting and densitometry analysis. In eyes from HSK-susceptible C.AL-20 mice, a more diverse TCR V beta transcript usage pattern was detected as compared with that seen in HSK-resistant C.B-17 mice. V beta 8 family members were expressed in both strains of mice at days 11, 14 and 21 post-inoculation. By densitometry, at day 11, the intensity of expression of V beta 8.2 and V beta 8.3 message was significantly greater in the eyes of C.AL-20 mice; V beta 8.1 was expressed only in C.B-17 mice. There were obvious differences in the TCR V beta expression between HSK-susceptible and HSK-resistant mice. The differences in the intensity of the message expressed by V beta 8 family members between the two strains could be correlated to previous experiments that showed V beta 8.1,2+ T cells as the main infiltrating cells in the corneas of HSK-susceptible mice by day 11 and 14 after challenge with HSV-1.
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PMID:T cell receptor V beta gene expression in experimental herpes stromal keratitis. 854 80

To examine the importance of B cells in the regulation of the T cell response to herpes simplex virus (HSV) infection, we have analyzed the selection of the T cell receptor (TCR) repertoire in C.B-17 mice that lack B cells (B. mice) compared with age-matched immunocompetent C.B-17 mice, usually resistant to herpes simplex keratitis (HSK). TCR V beta transcripts used by these mice were analyzed by polymerase chain reaction (PCR) with variable gene-specific primers. Clinical examination showed that the incidence of HSK was significantly different between untreated (control) and anti-mu antibody (Ab)-treated mice (p < 0.0001). Passive transfer of anti-HSV Ab into B. mice, before infection, prevented HSK; transfer of naive B cells allowed HSK to evolve in 50% of these mice. AT the level of gene expression, we demonstrated that the anti-mu Ab treatment altered TCR V beta gene expression in eyes, spleen, thymus and lymph nodes (LN) of C.B-17 mice. Preferential utilization of a single TCR Tb gene was not detected in the course of the disease except in LN, although in resistant mice there were different patterns of mRNA induction in T cells expressing specific TCR Vb elements that were not seen in susceptible mice, namely the lack of expression of V beta 8.1, V beta 8.2 and V beta 8.3 in eyes, the expression of V beta 7 in spleen, and the lack expression of V beta 6 and V beta 13 in thymus. These observations together with previous findings suggest that at the level of protein production, anti-HSV Ab not only can provide protection against HSK but is also a critical component for protection against HSV in normally resistant C.B17 mice, and that a dysregulation of the immune system in B. mice is manifested by dramatic changes in TCR V beta usage at the molecular level.
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PMID:Analysis of T cell receptor V beta gene expression in B cell deficient mice after experimental herpes simplex virus keratitis. 938 2

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

Viruses are suspected but usually unproven triggering factors in autoimmunity. One favored mechanism to explain the role of viruses in the genesis of autoimmunity is molecular mimicry. An immunoinflammatory blinding lesion called herpetic stromal keratitis (HSK) that follows ocular infection with herpes simplex virus (HSV) is suggested to result from a CD4(+) T-cell response to a UL6 peptide of HSV that cross-reacts with a corneal autopeptide shared with the immunoglobulin G2a(b) (IgG2a(b)) isotype. The present report reevaluates the molecular mimicry hypothesis to explain HSK pathogenesis. Our results failed to reveal cross-reactivity between the UL6 and IgG2a(b) peptides or between peptide reactive T cells and HSV antigens. More importantly, animals infected with HSV failed to develop responses that reacted with either peptide, and infection with a recombinant vaccinia UL6 vector failed to cause HSK, in spite of generating UL6 reactivity. Other lines of evidence also failed to support the molecular mimicry hypothesis, such as the failure to affect HSK severity upon tolerization of susceptible BALB/c and B-cell-deficient mice with IgG2a(b) or UL6 peptides. An additional study system revealed that HSK could be induced in mouse strains, such as the OT2 x RAG1(-/-) mice (T cell receptor transgenic recognizing OVA(323-339)) that were unable to produce CD4(+) T-cell responses to any detectable HSV antigens. Our results cast doubt on the molecular mimicry hypothesis as an explanation for the pathogenesis of HSK and indicate that if autoimmunity is involved its likely proceeds via a bystander activation mechanism.
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PMID:Herpes simplex virus-induced keratitis: evaluation of the role of molecular mimicry in lesion pathogenesis. 1123 34

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