Peripheral blood T cell proliferative response to chlamydial organisms in gonococcal and non-gonococcal urethritis and presumed pelvic inflammatory disease.

OBJECTIVE: To study peripheral blood mononuclear cell (PBMC) proliferative response to Chlamydia trachomatis elementary bodies in (a) controls, (b) various stages of gonococcal (c) and non-gonococcal urethritis, and (d) women with a clinical diagnosis of pelvic inflammatory disease (PID). METHODS: We categorised 102 men presenting to a GUM clinic with urethritis by organisms (C trachomatis (CT) or Neisseria gonorrhoeae (NG) (both by culture), and whether it was their first (urethritis naive) or subsequent (urethritis experienced) attack. 23 women presenting to the clinic with a clinical diagnosis of PID were also investigated. We measured PBMC proliferative responses to C trachomatis (DK20--an oculogenital strain, serovar E), lysate of McCoy cells (used to propagate chlamydiae), and the recall antigen PPD. Controls were 37 men and women without present or past history of urethritis or chlamydial infection. Results were expressed as the ratio of the stimulation index (SI) obtained with DK20 compared with McCoy cells (DK index), and the ratio of the SI obtained with DK20 compared with PPD (PPD index). RESULTS: The median SI to DK20 in the urethritis was 12.7 which was significantly higher than the controls (7.6, p < 0.003). The median SI to the recall antigen PPD was similar in the urethritis patients (17.4) and the controls (22.4). All urethritis patient subgroups had a significantly higher DK index and PPD index than the controls. There was no difference in the PPD and DK index between urethritis naive and urethritis experienced patients and between the culture positive and culture negative urethritis subgroups. In PID patients only the PPD index was significantly higher than the controls. CONCLUSION: Men presenting with urethritis and women presenting with PID both have significantly greater peripheral blood mononuclear cell proliferative responses to the DK20 strain of C trachomatis than controls. A similar T cell proliferative response pattern in urethritis naive patients with either gonococcal or non-gonococcal urethritis could be because low sensitivity of CT culture failed to diagnose some cases of C trachomatis. However, it may also signify earlier exposure of the patients to chlamydial antigens (for example, C pneumoniae), cross reacting antigens such as heat shock proteins from other microbial species, or a "bystander" activation of chlamydia specific memory T cells trafficking through mucosal lymphoid tissue during urethritis. These results suggest evidence of T cell mediated response to C trachomatis cannot be used as a diagnostic tool.

Isolation and characterisation of T lymphocytes from the urethra of patients with acute urethritis.

OBJECTIVES: To investigate local cellular immune responses in patients with acute urethritis. METHODS: We have established T cell lines from the urethral exudate and examined their phenotype by flow cytometry. As controls, T cell lines were cultured from first pass urine specimens of asymptomatic healthy individuals. RESULTS: Using interleukin 2 (IL-2) alone a T cell line was obtained on only one occasion. Following culture with IL-2, and subsequent expansion by a single stimulation with irradiated allogenic peripheral blood mononuclear cells (PBMC), phytohaemagglutinin (PHA), and IL-2, it was possible to establish T cell lines from 6/6 acute urethritis patients. T cell lines were also obtained from 4/12 controls subjects, but required repetitive rounds of stimulation with mitogen and allogeneic PBMC to produce sufficient cell numbers for analysis. Three of the patient T cell lines were dominated by T cells expressing the gamma delta receptor. CONCLUSION: The gamma delta T cell subset has been associated with immune responses at mucosal surfaces and has the ability to recognise certain bacterial antigens. The gamma delta T cell response may represent an important aspect of the immune response to organisms associated with acute urethritis.