Recognition of the 60 kilodalton cysteine-rich outer membrane protein OMP2 by CD4(+) T cells from humans infected with Chlamydia trachomatis.

T cell-mediated immunity is important in the control of chlamydia infection but chlamydia-specific T cells are also implicated in the inflammation and tissue damage which characterize chlamydia associated diseases. To investigate target antigens of the T cell-mediated immune response to chlamydia infection, Chlamydia trachomatis-specific CD4+ T cell clones were isolated from a patient with chlamydia-induced reactive arthritis. T cell immunoblotting indicated that an antigen of approximately 60 kilodaltons molecular mass was recognized, and recombinant 60 kilodalton cysteine-rich outer membrane 2 (OMP2) proved to be stimulatory. By using deletion constructs and synthetic peptides an epitope presented by HLA-DRB1*0401 was defined and proved to contain the nonamer peptide within the OMP2 sequence predicted to have the greatest binding affinity for DRB1*0401 The sequence of the epitope is conserved in all C. trachomatis strains but not in C. pneumoniae. Investigation of patients with acute urethritis and additional patients with sexually acquired reactive arthritis showed that OMP2-reactive T cells were readily detectable in peripheral blood and synovial fluid. Thus OMP2 is a target antigen of the T cell-mediated immune response to CT infection.

Conserved TcR beta chain usage for a single MHC class II-restricted heat shock protein peptide.

Previously we have shown that the T-cell response against the HLA-DR3 (17)-restricted heat shock protein (Mr 65 000)-derived peptide amino acids (aa) 3-13 (hsp65 aa 3-13) is recognized by the exclusive usage of the TRBV5 gene as well as a conserved CDR3 region in a tuberculoid leprosy patient. In the present study we analyzed the TcR of T-cell clones specific for hsp65 aa 3-13 derived from three healthy individuals with a response level similar to that of the leprosy patient. We show that unlike the tuberculoid leprosy patient, healthy high responders have a diverse T-cell response to hsp65 aa 3-13. However, a striking observation was made: even though high responders have a diverse specific TcR repertoire, TRBV5-expressing clones from two healthy individuals could be isolated that were nearly identical to a dominant clone in the tuberculoid leprosy patient. In conclusion, the data show that restriction of TcR specific for an antigen correlates with the presence of that antigen in disease. However, the preferred TcR can also be detected in healthy high responders. A natural infection in vivo, as with the tuberculoid leprosy patient, may be responsible for the observed trimming and preferential outgrowth of a certain TcR.

Analysis of T cell subsets present in the peripheral blood and synovial fluid of reactive arthritis patients.

OBJECTIVE: Reactive arthritis (ReA), a HLA-B27 associated arthropathy, develops in susceptible people after infection with certain bacteria. T cells have been implicated in the pathogenesis of the arthritis but which of the different subsets is involved is still debated. This study has further elucidated the role of the CD4+ and CD8+ T cells by examining the expression of various surface markers associated with activation. METHODS: Three colour flow cytometry was used to examine the phenotype of the T cells within the synovial fluid (SF) and peripheral blood (PB) of ReA patients. RESULTS: ReA SF, compared with paired PB, contained a higher percentage of CD69+, CD25+, and HLA-DR+ CD3+ T cells. The majority of SF T cells also expressed the putative memory marker CD45RO. Within the T cell subsets, CD25 was expressed primarily on the CD4+ T cells; however more CD8+ T cells were HLA-DR+. CONCLUSION: The results show that both CD4+ and CD8+ T cell populations demonstrate evidence of recent activation. Whether these cells are involved in inducing inflammation, regulating the inflammation, or have become active as a result of migration through the endothelium, remains to be determined by functional studies.

Human gamma delta T-cell recognition of Yersinia enterocolitica.

We have studied the human gamma delta T-cell response to Yersinia enterocolitica, a facultative intracellular bacterium which causes gastroenteritis and, particularly in human leucocyte antigen (HLA)-B27+ individuals, reactive arthritis (ReA). A marked proliferation of that cytotoxic gamma delta T cells is seen when Yersinia-infected lymphoblastoid cell lines or fixed intact Yersinia are added to cultures of mononuclear cells derived from the synovial fluid of ReA patients or from the peripheral blood of healthy donors. In contrast, heat-inactivated Yersinia fail to stimulate the gamma delta T-cell response. The gamma delta T-cell lines generated killed both autologous and allogeneic infected cell lines. Interestingly, a T-cell line generated from synovial fluid mononuclear cells (SFMC) killed infected autologous cell lines and a cell line matched for HLA-B27 less well than infected allogeneic target cells. gamma delta T-cell clones isolated from this line were found to express V gamma 9V delta 2 T-cell receptor (TCR) and also killed infected mismatched cells more efficiently than autologous targets. Moreover, from experiments using major histocompatability complex (MHC)-deficient cell lines, it was apparent that target cell recognition was MHC independent. Our results suggest that gamma delta T cells can be involved in immunity to Yersinia enterocolitica and should be taken into account when considering immunopathological mechanisms leading to reactive arthritis.