Human papillomavirus reactivation following treatment of genital graft-versus-host disease.

Vaginal chronic graft-versus-host disease (cGVHD) is a common complication of stem cell transplantation. Human papillomavirus (HPV) disease can reactivate after transplantation, presumably because of immune factors affecting systemic immunity, such as waning antibody titers, impaired T- and B-lymphocyte responses, and the use of immunosuppressive therapies. However, a relationship between the use of local immunosuppressive agents and HPV reactivation and spread has not been previously described, to our knowledge. A 30-year-old woman, 2 years post transplant receiving systemic cyclosporine for cGVHD, was treated with vaginal dilators, topical corticosteroids, and estrogen for vaginal cGVHD. Colposcopy and biopsy for abnormal cytology revealed condylomatous cervicitis. Over the next 4 months, while continuing dilator therapy, linear verrucous lesions developed in the vagina and vulva, and were successfully treated with laser therapy. Use of local immunosuppression and dilators for genital GVHD can enhance spread of HPV infection. Integration of HPV screening and treatment into the care of women with genital cGVHD and development of strategies to manage both conditions simultaneously are warranted.

Persistent Mycoplasma genitalium infection of human endocervical epithelial cells elicits chronic inflammatory cytokine secretion.

Infection with Mycoplasma genitalium has been associated with male and female urogenital disease syndromes, including urethritis, cervicitis, pelvic inflammatory disease (PID), and tubal factor infertility. Basic investigations of mucosal cytotoxicity, microbial persistence, and host immune responses are imperative to understanding these inflammatory urogenital syndromes, particularly in females, considering the potential severity of upper tract infections. Here, we report that M. genitalium can establish long-term infection of human endocervical epithelial cells that results in chronic inflammatory cytokine secretion and increased responsiveness to secondary Toll-like receptor (TLR) stimulation. Using a novel quantitative PCR assay, M. genitalium was shown to replicate from 0 to 80 days postinoculation (p.i.), during which at most time points the median ratio of M. genitalium organisms to host cells was ≤10, indicating that low organism burdens are capable of eliciting chronic inflammation in endocervical epithelial cells. This observation is consistent with clinical findings in women. Persistently secreted cytokines predominately consisted of potent chemotactic and/or activating factors for phagocytes, including interleukin-8 (IL-8), monocyte chemotactic protein 1 (MCP-1), and macrophage inflammatory protein 1ß (MIP-1ß). Despite persistent cytokine elaboration, no host cell cytotoxicity was observed except with superphysiologic loads of M. genitalium, suggesting that persistent infection occurs with minimal direct damage to the epithelium. However, it is hypothesized that chronic chemokine secretion with leukocyte trafficking to the epithelium could lead to significant inflammatory sequelae. Therefore, persistent M. genitalium infection could have important consequences for acquisition and/or pathogenesis of other sexually transmitted infections (STIs) and perhaps explain the positive associations between this organism and human immunodeficiency virus (HIV) shedding.

Interactions of metabolism, inflammation, and reproductive tract health in the postpartum period in dairy cattle.

This paper reviews recent data and concepts on the development of inflammation in the reproductive tract of dairy cows during the first 2 months after calving. The incidence of metritis is typically 10-20%, with 5-15% of cows having purulent vaginal discharge (PVD), 15-40% having cervicitis approximately 1 month after calving, and 10-30% having cytological endometritis between 1 and 2 months after calving. Endometritis, cervicitis and PVD are distinct conditions, each of which is associated with significantly increased time to pregnancy, and affected cows often have more than one of these conditions. Cumulatively, 35-50% of cows have at least one form of pathological reproductive tract inflammation between 3 and 7 weeks postpartum. It is hypothesized that reproductive tract disease represents a failure of the immune system to switch fast enough or far enough from the down-regulated state necessary for maintenance of pregnancy to a heightened state of function for postpartum clearance of bacteria and tissue debris and then to a 'quiet' state 3-4 weeks later. There are numerous links between fat metabolism, inflammation and immune function, and changes in these precede reproductive tract disease by several weeks. An excessive pro-inflammatory state early in the postpartum period appears to be a key feature of cows with endometritis approximately 1 month later. Generally, worse postpartum negative energy balance (NEB) is associated with more severe or prolonged uterine inflammation. Aspects of both mononuclear cell proliferation and neutrophil oxidative burst are commonly impaired, particularly in association with elevated non-esterified fatty acid concentrations and to a lesser degree by ketosis. In summary, NEB contributes to immune dysfunction which in turn is a major component of reproductive tract inflammatory disease. The factors that initiate and sustain harmful inflammation of the reproductive tract are not yet well quantified.

[Detection of the interferon deficiency in inflammatory gynecological diseases and its correction with interferon inducers].

Interferons deficiency has a negative influence on the development of infection and inflammation in general. The use in the complex of anti-inflammatory therapy of interferon inducers (Meglumine acridоnacetate, Tilorone), combining antiviral, immunomodulatory, interferon correction effects with etiopathogenic action leads to the correction of the interferon system defects and eliminate etiological infectious agents, that is confirmed by laboratory data and clinical efficacy.

[Correlation between human papillomavirus type 16 infection and human leukocyte antigen class I expression in cervical cancers of Uighur women].

OBJECTIVE: To explore the relationship between human papillomavirus(HPV) infection and expression of human leukocyte antigen class I (HLA-I) family genes (HLA-A, B and C) in cervical cancers of Uighur women, and to investigate their effect on cervical cancer progression. METHODS: Fresh tissue samples of 78 Uighur women with cervical squamous carcinoma, cervical intraepithelial neoplasia (CIN) or benign cervicitis were selected. HLA-A, B and C expression and HPV infection were analyzed using RT-PCR and HPV gene chips, respectively. RESULTS: There was a tendency of increasing the total loss of HLA-A, B and C mRNA as the cervical lesions became more aggressive. Loss of HLA-I mRNA in CIN (I, II and III) and cervical squamous carcinoma was 70.0% (14/20) and 84.8% (39/46) respectively. Poorly differentiated cervical carcinomas had the highest HLA-I expression loss (90.6%). In contrast, HLA-I mRNA loss was seen in only 8% of cases of cervicitis. Moreover, it was found that high risk HPV 16 infection was strongly correlated with the loss HLA-I mRNA expression (r = 0.803, P < 0.01). CONCLUSIONS: The loss of HLA-I gene expression is strongly correlated with HPV-16 infection, and may serve as a biomarker of cervical cancer progression in Uighur women.

Impact of mucosal inflammation on cervical human immunodeficiency virus (HIV-1)-specific CD8 T-cell responses in the female genital tract during chronic HIV infection.

The female genital tract is the major route of heterosexual human immunodeficiency virus (HIV) acquisition and transmission. Here, we investigated whether HIV-specific CD8 T-cell-mediated immune responses could be detected in the genital mucosa of chronically HIV-infected women and whether these were associated with either local mucosal HIV shedding or local immune factors. We found that CD8(+) T-cell gamma interferon responses to Gag were detectable at the cervix of HIV-infected women but that the magnitude of genital responses did not correlate with those similarly detected in blood. This indicates that ex vivo HIV responses in one compartment may not be predictive of those in the other. We found that increased genital tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) levels correlated significantly with levels of Gag-specific CD8(+) T cells at the cervix. Women who were detectably shedding virus in the genital tract had significantly increased cervical levels of TNF-alpha, IL-1beta, IL-6, and IL-8 compared to women who were not detectably shedding virus. We were, however, unable to detect any association between the magnitude of cervical HIV-specific responses and mucosal HIV shedding. Our results support the hypothesis that proinflammatory cytokines in the female genital tract may promote HIV replication and shedding. In addition, we further show that inflammatory cytokines are associated with increased levels of HIV-specific CD8 effector cells at the genital mucosa but that these were not able to control genital HIV shedding.

[Pathogenesis and clinical significance of interleukin-8 and tumor necrosis factor-alpha in cervicitis].

OBJECTIVE: To investigate the relationship between local immune status of vagina and the occurrence of disease in patients with cervicitis. METHODS: ELISA were used to detect the level of interleukin (IL)-8 and tumor necrosis factor (TNF)alpha in vaginal douche of patients with cervicitis due to ureaplasma urealyticum, mycoplasma hominis, chlamydia trachomatis, neisseria gonorrhoeae and cervical erosion. RESULTS: Compared with the control group, the level of IL-8 in vaginal douche of patients with mycoplasma hominis cervicitis, chlamydia trachomatis cervicitis and neisseria gonorrhoeae cervicitis was significantly higher and there was significant difference ng/L: 371 +/- 34, 369 +/- 31, 339 +/- 36, vs 341 +/- 32, 338 +/- 33, 316 +/- 24, (all P < 0.01). Comparing the level of IL-8 in vaginal douche of patients with ureaplasma urealyticum cervicitis and cervical erosion with that of control group, there was no statistical difference (all P > 0.05). The level of TNF-alpha in vaginal douche of each group was remarkably higher than that of control group except for patients with cervical erosion. And statistically significant difference was found between them (all P < 0.01). CONCLUSION: With regards to the pathogenesis of cervicitis, local immune mechanism of vagina plays an important role in the occurrence of cervicitis. The role of IL-8 in pathogenesis of mycoplasma hominis cervicitis, chlamydia trachomatis cervicitis and neisseria gonorrhoeae cervicitis is likely to be more important.

[Study of local immunity of lower genital tract infections].

OBJECTIVE: To investigate the profile of local immunity of vagina and the immune defense mechanisms against lower genital tract infections. METHODS: Vaginal lavage was collected from healthy women and patients of vulvovaginal candidiasis, bacterial vaginosis, Trichomonol vaginitis, human papilloma virus infection (VVC), and chlamydia trachomatis infection. Each group included 60 cases. The level of interleukin (IL)2, 4, 5, 13, 8 and human defensin 5 (HD5) were detected by enzyme linked immunosorbent assay(ELISA). RESULTS: (1) Cytokine of helper T cell 1(Th1): the level of IL-2 between healthy women and VVC/ bacterial vaginosis (BV)/ trichomonol vaginitis (TV)/ chlamydia trachomatis (CT) patients had no significant difference. The IL-2 level(96 +/- 33) x 10(-3) pg/L of human papilloma virus (HPV) infection patients was significantly higher than that of healthy women (P < 0.05). (2) Cytokine of helper T cell 2 (Th2): the level of IL-4 between healthy women and VVC/CT patients had no significant difference. The level of IL-5 between healthy women and BV patients had no significant difference. The IL-13 level (42 +/- 15) x 10(-3) pg/L of TV patients was significantly higher than that of healthy women (30 +/- 29) x 10(-3) pg/L (P < 0.05). The IL-4 level (103 +/- 28) x 10(-3) pg/L of HPV infection patients was significantly higher than that of healthy women (36 +/- 22) x 10(-3) pg/L (P < 0.05). (3) IL-8: the IL-8 level (5.8 +/- 2.7) pg/L of TV infection patients was significantly higher than that of healthy women (2.6 +/- 2.4) pg/L (P < 0.05). The level of IL-8 between healthy women and BV patients had no significant difference. (4) HD5: the HD5 level of TV, BV, VVC, HPV and CT infection patients were significantly higher than that of healthy women (P < 0.05). CONCLUSIONS: (1) HD5 plays an important role in the defence of vaginal epithelial cell. (2) Th2 may be more important than Thl in lower genital tract infections. (3) IL-8 plays an important role in extrinsic source infections.

Radiation induces changes in toll-like receptors of the uterine cervix of the rat.

Radiotherapy is an important therapeutic approach against cervical cancer but associated with adverse effects including vaginal fibrosis and dyspareunia. We here assessed the immunological and oxidative responses to cervical irradiation in an animal model for radiation-induced cervicitis. Rats were sedated and either exposed to 20 Gy of ionising radiation given by a linear accelerator or only sedated (controls) and euthanized 1-14 days later. The expressions of toll-like receptors (TLRs) and coupled intracellular pathways in the cervix were assessed with immunohistofluorescence and western blot. Expression of cytokines were analysed with the Bio-Plex Suspension Array System (Bio-Rad). We showed that TLRs 2-9 were expressed in the rat cervix and cervical irradiation induced up-regulation of TLR5, TRIF and NF-κB. In the irradiated cervical epithelium, TLR5 and TRIF were increased in concert with an up-regulation of oxidative stress (8-OHdG) and antioxidant enzymes (SOD-1 and catalase). G-CSF, M-CSF, IL-10, IL- 17A, IL-18 and RANTES expressions in the cervix decreased two weeks after cervical irradiation. In conclusion, the rat uterine cervix expresses the TLRs 2-9. Cervical irradiation induces immunological changes and oxidative stress, which could have importance in the development of adverse effects to radiotherapy.

Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis.

OBJECTIVES: To compare cervical concentrations of numerous cytokines/chemokines in women with bacterial vaginosis (BV) compared with the levels detected after BV resolution and determine if hormonal contraceptive use modulates the local inflammatory response to BV. METHODS: Cervical secretions from 81 women with BV at enrollment and normal flora at one-month follow-up were analysed for 10 different cytokines/chemokines using multiplexed fluorescent bead-based immunoassays. RESULTS: BV was associated with significantly higher concentrations of IL-1 beta, tumour necrosis factor (TNF), interferon-gamma, IL-2, IL-4, and IL-10 compared with the levels detected in the presence of normal vaginal flora. Analysis of results stratified by contraceptive practice demonstrated significantly lower levels of numerous cytokines among women with BV using hormonal contraceptives compared with those women with BV not using hormonal contraceptives. Hormonal contraceptive use was also associated with a statistically significant lesser change in TNF levels between the two study visits compared with the amount of change detected between visits among women who denied their use. CONCLUSIONS: Despite increases in the levels of both pro and anti-inflammatory cytokines in the lower genital tract of women with BV, the overall balance of these two types of molecules was maintained. The character of this local inflammatory response may help explain the typical absence of overt signs of inflammation among women with BV. In addition, hormonal contraceptive use was associated with significantly lower levels of the pro-inflammatory molecules TNF, interferon-gamma, and granulocyte macrophage colony-stimulating factor in women with BV, but did not significantly reduce the levels of IL-10, a key anti-inflammatory cytokine. These results suggest the possibility of an association between hormonal contraceptive use and altered genital tract immunity.

In infertile women, cells from Chlamydia trachomatis infected sites release higher levels of interferon-gamma, interleukin-10 and tumor necrosis factor-alpha upon heat-shock-protein stimulation than fertile women.

BACKGROUND: The magnitude of reproductive morbidity associated with sexually transmitted Chlamydia trachomatis infection is enormous. Association of antibodies to chlamydial heat shock proteins (cHSP) 60 and 10 with various disease sequelae such as infertility or ectopic pregnancy has been reported. Cell-mediated immunity is essential in resolution and in protection to Chlamydia as well as is involved in the immunopathogenesis of chlamydial diseases. To date only peripheral cell mediated immune responses have been evaluated for cHSP60. These studies suggest cHSPs as important factors involved in immunopathological condition associated with infection. Hence study of specific cytokine responses of mononuclear cells from the infectious site to cHSP60 and cHSP10 may elucidate their actual role in the cause of immunopathogenesis and the disease outcome. METHODS: Female patients (n = 368) attending the gynecology out patient department of Safdarjung hospital, New Delhi were enrolled for the study and were clinically characterized into two groups; chlamydia positive fertile women (n = 63) and chlamydia positive infertile women (n = 70). Uninfected healthy women with no infertility problem were enrolled as controls (n = 39). cHSP60 and cHSP10 specific cytokine responses (Interferon (IFN)-gamma, Interleukin (IL)-10, Tumor Necrosis Factor (TNF)-alpha, IL-13 and IL-4) were assessed by ELISA in stimulated cervical mononuclear cell supernatants. RESULTS: cHSP60 and cHSP10 stimulation results in significant increase in IFN-gamma (P = 0.006 and P = 0.04 respectively) and IL-10 levels (P = 0.04) in infertile group as compared to fertile group. A significant cHSP60 specific increase in TNF-alpha levels (P = 0.0008) was observed in infertile group as compared to fertile group. cHSP60 and cHSP10 specific IFN-gamma and IL-10 levels were significantly correlated (P < 0.0001, r = 0.54 and P = 0.004, r = 0.33 respectively) in infertile group. CONCLUSION: Our results suggest that exposure to chlamydial heat shock proteins (cHSP60 and cHSP10) could significantly affect mucosal immune function by increasing the release of IFN-gamma, IL-10 and TNF-alpha by cervical mononuclear cells.

[Streptococcus group B--association with Aerobic vaginitis and ability to human cell lines activation]. / Paciorkowce grupy B--zwiazek z Aerobic vaginitis oraz zdolnosc do aktywacji ludzkich linii komórkowych.

The aim of this study was to estimate: the frequency of aerobic vaginitis, susceptibility of the GBS isolated from vagina of non-pregnant women with and without cervicitis to selected antibiotics and chemotherapeutics and the proinflammatory cytokines production by HeLa, THP-I, U - 937 cells after stimulation by vaginal GBS. Our results indicated low frequency of the aerobic vaginitis -4.5% among non-pregnant young women and ability of the vaginal GBS to release proinflammatory cytokines by human cell lines in vitro.

Demonstration and characterization of the angiogenic properties of cervical dysplasia.

Cervical dysplasia, or cervical intraepithelial neoplasia (CIN), is a premalignant precursor to cervical cancer. This study was designed to determine whether dysplastic lesions are angiogenic. Tissue sections from 23 surgical specimens were immunohistochemically stained for factor VIII antigen, a marker for endothelial cells. The results demonstrate that a region of neovascularization develops along the basement membrane subtending dysplastic epithelium when compared to adjacent normal epithelium. Comparison of microvessel counts underlying low grade lesions (condyloma and CIN I) with microvessel counts of CIN III lesions shows a statistically significant increase in the more advanced lesions. In a subset of the high grade lesions, large vascular structures are also noted in the upper layers of the epithelium, suggesting that a second stage of neovascularization consists of extension of stromal vascular papillae into the dysplastic lesions toward the surface of the epithelium. There is no statistical correlation between the amount of inflammation and the angiogenic ratio for each lesion, implying that angiogenesis is not secondary to the inflammatory response evoked by the lesion. The human papillomavirus type present in four CIN III lesions was determined by in situ hybridization; the amount of angiogenesis appears to be independent of the human papillomavirus type.

[Immunological indices in differential diagnosis of active and inactive chronic endocervicitis].

A total of 132 patients were examined for chronical endocervicitis by clinical, immunological and morphological methods. According to the results obtained the patients were subdivided into several groups. The first group covered 77 females with an active clinical somatic form of the disease. The second group included 55 patients with chronical inactive endocervicitis. Controls included 25 practically healthy females. No differences were found between immunological indices of peripheral blood in groups of patients with active and inactive forms of chronic endocervicitis. Immunological tests on cervical mucus in patients with chronic endocervicitis revealed differences in the total number of leukocytes, content of living cells, functional activity of neutrophils, concentration of immunoglobulins and proinflammatory cytokines. This study may contribute to the development of immunological criteria for diagnosis of inflammatory process activity as well as a diagnostic model.

[Immunological and microbiological aspects of low intensity laser effect on the factors of local immunity of the reproductive tract in women with chlamydia infection].

Assessment of immunological and microbiological efficacy of Chlamydia cervicitis management was made by a complex method with a low intensity laser. The total number of leukocytes, percentage of viable cells and the number of neutrophils were detected in cervical secrets. Functional status of neutrophils was studied by a content of lysosomes on the ground of spontaneous and induced by latex HCT-reducing capacity, phagocytic activity. A system of cytokines was studied by interleukine level (IL-1 alpha, IL-1 beta, TNF-alpha, IL-8) and IFN-gamma content in cervical mucus. Positive clinical effect of the local use of the low intensity laser for Chlamydia cervicitis treatment was accompanied by positive changes in immunological indices of cervical secret, normal concentration of cytokines in cervical secret, restoration of the number and functions of neutrophils. Local use of the low intensity laser contributed to decreased number of opportunistic pathogenic microorganisms and their associations, and restored local flora.

Occurrence of antibodies against chlamydial lipopolysaccharide in human sera as measured by ELISA using an artificial glycoconjugate antigen.

An artificial glycoconjugate containing, as a ligand, the deacylated carbohydrate backbone of a recombinant Chlamydia-specific lipopolysaccharide was used as a solid-phase antigen in ELISA to measure antibodies against chlamydial LPS. The specificity and reproducibility of the assay was shown by using a panel of prototype monoclonal antibodies representing the spectrum of antibodies also occurring in patient sera. These mAbs recognized Chlamydia-specific epitopes [alpha 2-->8-linked disaccharide of 3-deoxy-D-manno-octulosonic acid (Kdo) or the trisaccharide alpha Kdo-(2-->8)-alpha Kdo-(2-->4)-alpha Kdo] or those shared between chlamydial and Re-type LPS (alpha Kdo, alpha 2-->4-linked Kdo disaccharide). The assay was used to measure IgG, IgA and IgM antibodies against chlamydial LPS in patients with genital or respiratory tract infections. In comparison to the results obtained with sera from blood donors, it became evident that both types of infection result in significant changes in the profile of LPS antibodies.

Cervical smear total IgA in adenomatous polyp, dysplasia and carcinoma of the cervix.

Cervical smear total IgA (IgAc) concentration was determined in cervicitis and proliferative disorders of the cervical epithelium. All disorders except adenomatous polyp showed increased median IgAc levels as compared with healthy controls, in both the reproductive and the postmenopausal ages. In the former age group dysplasia exhibited the highest median IgAc level, while in the latter it ranked, second following specific cervicitis. Though differences between disease groups and controls were statistically non significant, they attained percent values as large as +277% (dysplasia, postmenopausal) and +596.9% (specific cervicitis, postmenopausal). Separate quantitation of the dimeric secretory and monomeric serum-derived components of total IgAc will provide more meaningful information.

Enhanced immunocompetent cells in chlamydial cervicitis.

OBJECTIVE: To investigate changes in cell-mediated immunophenotypes by flow cytometry in endocervical secretions and peripheral blood in women with Chlamydia trachomatis infection. STUDY DESIGN: Fifty women attending the gynaecology outpatient department of Safdarjang Hospital, New Delhi, India, with signs and symptoms of cervicitis were enrolled. All patients underwent endocervical screening for C trachomatis (direct fluorescence antibody test [DFA]), and any coinfection with Candida (Gram stain), bacterial vaginosis (Gram stain), Neisseria gonorrhoeae (Gram stain), Trichomonas vaginalis (wet mount) and HIV (enzyme-linked immunosorbent assay) was ruled out. Flow cytometry was done to investigate changes in immunophenotypes in endocervical secretions and peripheral blood using monoclonal antibodies for surface markers (CD3, CD4, CD8, CD19, CD45 and CD83). Data were analyzed by chi2 test, while means were compared using Student's t test. RESULTS: C trachomatis positivity was found to be 36% (n = 18). Forty-eight patients constituted the study population since 2 patients coinfected with Candida, bacterial vaginosis and T vaginalis were excluded. A statistically significant enhancement in CD4+, CD8+ and dendritic cellular phenotypes was observed in the endocervical secretions of Chlamydia-positive patients, while B cells showed no marked difference. In the parallel study of matched peripheral blood, immunophenotypes did not show statistically significant results. CONCLUSION: Increased influx of CD4+, CD8+ and dendritic cells in the endocervix is an indication of cell-mediated immunity in response to C trachomatis infection. Local immune response in the cervical region is independent of systemic response. The mechanism by which local mucosal and systemic immune cells interact to repel or enhance susceptibility to C trachomatis infection requires further study.

Immunocytochemical demonstration of Chlamydia infection in the urogenital tracts.

The peroxidase-antiperoxidase (PAP) technique was applied in cellular samples for the detection of chlamydial infection. Urethral scrapings were obtained from 316 males with clinically suspected urethritis. Positive PAP staining was detected in 118 (37%) of 316 tested. Cellular samples from the endocervix of 25 (54%) of 46 female contacts of males with positive Chlamydia-infected cells had positive Chlamydia-PAP staining. Chlamydia was also found in 12 (25%) of 48 male with gonorrhea. Serum IgG antibodies against Chlamydia trachomatis were evaluated using an enzyme-linked immunosorbent assay. A total of 29 out of 73 patients had positive Chlamydia serology; of these, 21 were positive for PAP staining, and eight were negative. The determination of Chlamydia antigen by means of the PAP technique appears to be a satisfactory method for detecting Chlamydia in male and female genital specimens; also, the procedure can be done readily in most laboratory settings.

Host immune response in chlamydial cervicitis.

In order to study host immune responses to Chlamydia trachomatis infection in patients with chlamydial cervicitis, lymphoproliferative responses to purified protein derivative (PPD) and Chlamydia trachomatis antigen (elementary bodies) were studied in 15 patients and 10 normal control subjects. A significant lymphoproliferation of peripheral blood mononuclear cells (PBMC) was obtained with PPD and C. trachomatis antigen (P < 0.001) as compared to unstimulated PBMC showing that antigen-reactive T-cells are present in patients. There was no significant difference in the lymphoproliferation response to C. trachomatis in patients as compared to control subjects suggesting that the cell-mediated immune (CMI) response in peripheral blood is not altered in chlamydial cervicitis. Inhibition of IL-2 production in cervical secretions ranged from 44 to 84% in patients with chlamydial cervicitis while supernatants derived from PBMC stimulated with PPD failed to show inhibition. However, there was no inhibition of IL-2 production in secretion or supernatants stimulated with PPD in control subjects, thereby showing that local cell-mediated immunity is impaired in patients. Significant C. trachomatis specific IgA antibodies, in cervical secretions, were present in only three of 15 patients. C. trachomatis specific IgG, IgM and IgA were detected in the serum of most patients, suggesting that serum antibodies do not confer immunity at the local site. We conclude that although circulating antigen-reactive T-cells are present in chlamydial cervicitis patients, absence of protective antibody as well as impairment of local cell-mediated immunity may be responsible for alteration of the mucosal defence mechanism against chlamydial infection.