Association of major histocompatibility complex determinants with the development of symptomatic and asymptomatic genital herpes simplex virus type 2 infections.
(1/593)
The clinical spectrum of herpes simplex virus (HSV) infections, ranging from asymptomatic to frequently distressing outbreaks, suggests that there may be immunologic determinants of disease severity that are associated with human leukocyte antigen (HLA) expression. A controlled, prospective study identified several major histocompatibility complex (MHC) class I and II antigens whose frequencies are associated with HSV-2 infection or with frequent symptomatic genital recurrences. Previous studies were hampered by the inability to serologically identify patients with asymptomatic HSV-2 infection. Clinical evaluation and Western blot assay were used to identify 3 subject cohorts: 1 with no prior HSV infections, 1 with HSV-2 antibodies but no recognized symptoms, and 1 with HSV-2 antibodies and frequent genital recurrences. Statistical comparisons of HLA frequencies among these cohorts showed associations of HLA-B27 and -Cw2 with symptomatic disease. Also, HLA-Cw4 was significantly associated with HSV-2 infection. These associations indicate that immunologic factors linked to the MHC influence the risk of HSV-2 infection and disease expression. (+info)
Common intra-articular T cell expansions in patients with reactive arthritis: identical beta-chain junctional sequences and cytotoxicity toward HLA-B27.
(2/593)
Spondyloarthropathies constitute a group of autoimmune diseases of special interest because of their tight association with the MHC class I molecule HLA-B27 and the bacterial triggering of some clinical forms called reactive arthritis (ReA). One current hypothesis is the presentation by HLA-B27 of a so-called arthritogenic peptide to T cells. To better focus on the relevant T cell populations within the joint, we performed an extensive beta-chain T cell repertoire analysis of synovial fluid compared with PBL in seven patients, four of whom were characterized as having ReA triggered by Yersinia enterocolitica, Chlamydia trachomatis, or Shigella sonnei. Analysis of the size diversity of the beta-chain complementarity-determining region 3 (CDR3) allowed us to evaluate the degree of T cell clonality in the samples. Oligoclonal T cell expansions were frequently observed in the joint. In one patient, CDR3 amino acid sequences of major expansions using two different BV genes were identical. One dominant T cell expansion and several CDR3 amino acid sequences were identical in two different patients. Furthermore, one sequence was identical with a sequence reported independently in a Salmonella-induced ReA patient. Together, these data indicate a surprisingly high degree of conservation in the T cell responses in recent-onset ReA triggered by different micro-organisms. A CD8+ synovial line expressing shared clonotypes was established and reacted toward several B*2705 lymphoblastoid cell lines, therefore supporting a molecular mimicry phenomenon at the T cell level in the disease mechanism. (+info)
Pathogenesis of reactive arthritis.
(3/593)
Reactive arthritis is a member of the spondyloarthropathy. Bacteria which cause reactive arthritis infect the mucosal surfaces. Either the whole bacteria or their fragments are subsequently carried to the joints inside which are induced a TH1 lymphocyte response in which oligoclonal T lymphocytes as well peptide-specific CD8+ T lymphocytes participate. Human lymphocyte antigen (HLA)-B27 is a predisposing gene. Besides being determinants for the CD8+ T lymphocyte response it can also modify the response of other cells to the invasive bacteria. This would lead to alteration of the fate of the bacteria as well as release of arthritis-causing cytokines. (+info)
Cutting edge: HLA-B27 can form a novel beta 2-microglobulin-free heavy chain homodimer structure.
(4/593)
HLA-B27 has a striking association with inflammatory arthritis. We show that free HLA-B27 heavy chains can form a disulfide-bonded homodimer, dependent on residue Cys67 in their extracellular alpha 1 domain. Despite the absence of beta 2-microglobulin, HLA-B27 heavy chain homodimers (termed HC-B27) were stabilized by a known peptide epitope. HC-B27 complexes were recognized by the conformation-specific Ab W6/32, but not the ME1 Ab. Surface labeling and immunoprecipitation demonstrated the presence of similar W6/32-reactive free heavy chains at the surface of HLA-B27-transfected T2 cells. HC-B27 homodimer formation might explain the ability of HLA-B27 to induce spondyloarthropathy in beta 2-microglobulin-deficient mice. (+info)
Cell-surface expression and alloantigenic function of a human nonclassical class I molecule (HLA-E) in transgenic mice.
(5/593)
We have introduced the gene (E*01033) encoding the heavy chain of the human nonclassical MHC class I Ag, HLA-E, into the mouse genome. Two founder mice carry a 21-kb fragment, the others bear an 8-kb fragment. Each of the founder mice was mated to mice of an already established C57BL/10 transgenic line expressing human beta2-microglobulin (beta2m). Cell surface HLA-E was detected on lymph node cells by flow cytometry only in the presence of endogenous human beta2m. However, HLA-E-reactive mouse CTL (H-2-unrestricted) lysed efficiently the target cells originating from HLA-E transgenic mice without human beta2m, showing that the HLA-E protein can be transported to the cell surface in the absence of human beta2m, presumably by association with murine beta2m. Rejection of skin grafts from HLA-E transgenic mice demonstrates that HLA-E behaves as a transplantation Ag in mice. HLA-E transgenic spleen cells are effective in stimulating an allogeneic CTL response in normal and human classical class I (HLA-B27) transgenic mice. Furthermore, results from split-well analysis indicate that the majority of the primary in vivo-induced CTL recognizes HLA-E as an intact molecule (H-2-unrestricted recognition) and not as an HLA-E-derived peptide presented by a mouse MHC molecule, although a small fraction (ranging from 4 to 21%) of the primary in vivo-induced CTL is able to recognize HLA-E in an H-2-restricted manner. Based on these observations, we conclude that HLA-E exhibits alloantigenic properties that are indistinguishable from classical HLA class I molecules when expressed in transgenic mice. (+info)
Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli.
(6/593)
Resident bacteria play an important role in initiating and perpetuating gastrointestinal inflammation. We previously demonstrated that six commensal bacteria including Bacteroides vulgatus caused more aggressive colitis and gastritis in HLA-B27 transgenic rats than did the other five bacteria without B. vulgatus. This study compared the degree of gastrointestinal inflammation in gnotobiotic HLA-B27 transgenic rats monoassociated with either B. vulgatus or Escherichia coli. Gnotobiotic transgenic rats raised in Trexler isolators were selectively colonized with either B. vulgatus or E. coli. Control rats were either germfree or colonized with six common commensal bacteria (Streptococcus faecium, E. coli, Streptococcus avium, Eubacterium contortum, Peptostreptococcus productus, and B. vulgatus [DESEP-B]). After 1 month, all the rats were killed and tissues were prepared for histologic and biochemical evaluation. Colitis induced by B. vulgatus monoassociation was almost equal to that in DESEP-B-colonized rats and was significantly more severe than E. coli-induced colitis, which was absent by histological testing and mild by colonic myeloperoxidase and interleukin-1beta concentration determinations. However, gastritis was detectable only in DESEP-B-associated rats. These studies suggest that not all resident bacteria have equal proinflammatory capabilities, since B. vulgatus alone is more active than E. coli alone in inducing colitis, and that colitis and gastritis result from different luminal bacterial stimuli. (+info)
Chlamydia pneumoniae as a triggering infection in reactive arthritis.
(7/593)
OBJECTIVE: To determine the role of Chlamydia pneumoniae as a triggering infection in reactive arthritis (ReA). METHODS: Sixty patients with acute arthritis were screened for the evidence of triggering infections. In all patients, bacterial stool cultures, culture of Chlamydia trachomatis in urethra/cervix, and/or bacterial serology were studied. Chlamydia pneumoniae antibodies were measured by specific microimmunofluorescence test. RESULTS: Thirty-five of 60 patients fulfilled the diagnostic criteria for ReA. Thirty-one patients had microbial/serological evidence of preceding infection due to Salmonella, Yersinia, Campylobacter or Chlamydia trachomatis, or they had enteritis or urethritis prior to arthritis. Four additional patients had high antibody titre for C. pneumoniae. Three of these four patients had preceding lower respiratory symptoms, and were positive for HLA-B27. The clinical picture of C. pneumoniae-positive ReA patients was similar to that of ReA patients with other definite aetiology. CONCLUSION: Chlamydia pneumoniae is a triggering factor in approximately 10% of patients with acute ReA. (+info)
Human monocytic U937 cells kill Salmonella in vitro by NO-independent mechanisms.
(8/593)
Nitric oxide (NO) has a central role in host defense against intracellular microbes. HLA-B27 has been shown to directly modulate host-microbe interaction in vitro, leading to the impaired elimination of Salmonella in human monocytic U937 cells. Here, we studied whether impaired elimination of Salmonella would result from differences in NO production between HLA-B27- and HLA-A2-transfected U937 cells. Both human monocytic transfectants produced NO equally well and killed Salmonella via NO-independent mechanisms. (+info)