Stimulated peripheral blood mononuclear cells from chlamydia-infected women release predominantly Th1-polarizing cytokines

Chlamydia trachomatis infection (chlamydia) is the most prevalent sexually transmitted bacterial infection and causes significant reproductive morbidity in women. Little is known about how immunity to chlamydia develops in women, though animal models of chlamydia indicate that T-helper type 1 (Th1) responses are important for chlamydia clearance and protective immunity, whereas T-helper type 2 (Th2) responses are associated with persisting infection. In chlamydia-infected women, whether the predominant immune response is Th1- or Th2-polarizing remains controversial. To determine the cytokine profiles elicited by peripheral blood mononuclear cells (PBMCs) from chlamydia-infected women, we stimulated PBMCs with C. trachomatis elementary bodies and recombinant C. trachomatis Pgp3 and measured supernatant levels of select cytokines spanning Th1- and Th2-polarizing responses. We found that stimulated PBMCs from chlamydia-infected women secreted cytokines that indicate strong Th1-polarizing responses, especially interferon-gamma, whereas Th2-polarizing cytokines were expressed at significantly lower levels. In chlamydia-infected women, the predominant cytokine responses elicited on stimulation of PBMCs with C. trachomatis antigens were Th1-polarizing, with interferon-gamma as the predominant cytokine

Wide-Field Survey of Globular Clusters in M31. I. A Catalog of New Clusters

We present the result of a wide-field survey of globular clusters (GCs) in M31 covering a 3deg x 3deg field c. We have searched for GCs on CCD images taken with Washington CMT1 filters at the KPNO 0.9 m telescope using steps: (1) inspection of morphological parameters given by the SExtractor package such as stellarity, full maximum, and ellipticity; (2) consulting the spectral types and radial velocities obtained from spectra takena spectrograph at the WIYN 3.5 m telescope; and (3) visual inspection of the images of each object. We have and GC candidates, of which 605 are newly found GCs and GC candidates and 559 are previously known GCs. Amoects there are 113 genuine GCs, 258 probable GCs, and 234 possible GCs, according to our classification critee known objects there are 383 genuine GCs, 109 probable GCs, and 67 possible GCs. In total there are 496 genprobable GCs and 301 possible GCs. Most of these newly found GCs have T1 magnitudes of 17.5 - 19.5 mag, [17.9 < V < 19.9 mag assuming (C-T1) ~ 1.5], and (C-T1) colors in the range 1 - 2.Comment: accepted by AJ, using emulateapj.cl

An Adaptive Chlamydia trachomatis-Specific IFN-γ-Producing CD4+ T Cell Response Is Associated With Protection Against Chlamydia Reinfection in Women

Background: Adaptive immune responses that mediate protection against Chlamydia trachomatis (CT) remain poorly defined in humans. Animal chlamydia models have demonstrated that CD4+ Th1 cytokine responses mediate protective immunity against reinfection. To better understand protective immunity to CT in humans, we investigated whether select CT-specific CD4+ Th1 and CD8+ T cell cytokine responses were associated with protection against CT reinfection in women. Methods: Peripheral blood mononuclear cells were collected from 135 CT-infected women at treatment and follow-up visits and stimulated with CT antigens. CD4+ and CD8+ T-cells expressing IFN-γ, TNF-α, and/or IL-2 were assessed using intracellular cytokine staining and cytokine responses were compared between visits and between women with vs. without CT reinfection at follow-up. Results: A CD4+TNF-α response was detected in the majority (77%) of study participants at the treatment visit, but a lower proportion had this response at follow-up (62%). CD4+ IFN-γ and CD4+ IL-2 responses occurred less frequently at the treatment visit (32 and 18%, respectively), but increased at follow-up (51 and 41%, respectively). CD8+ IFN-γ and CD8+ TNF-α responses were detected more often at follow-up (59% for both responses) compared to the treatment visit (30% for both responses). At follow-up, a CD4+IFN-γ response was detected more often in women without vs. with reinfection (60 vs. 33%, P = 0.005). Conclusions: Our findings suggest that a CT-specific CD4+ IFN-γ response is associated with protective immunity against CT reinfection and is thus an important component of adaptive immunity to CT in women

Wide-Field Survey of Globular Clusters in M31. II. Kinematics of the Globular Cluster System

We present a kinematic analysis of the globular cluster(GC) system in M31. Using the photometric and spectroscopic database of 504 GCs, we have investigated the kinematics of the M31 GC system. We find that the all GC system shows strong rotation, with rotation amplitude of v_rot~190km/s, and that a weak rotation persists even for the outermost samples at |Y|>5kpc. The rotation-corrected velocity dispersion for the GC system is estimated to be sigma_{p,r}~130km/s, and it increases from sigma_{p,r}~120km/s at |Y|<1kpc to sigma_{p,r}~150km/s at |Y|>5kpc. These results are very similar to those for the metal-poor GCs. This shows that there is a dynamically hot halo in M31 that is rotating but primarily pressure-supported. We have identified 50 "friendless" GCs, and they appear to rotate around the major axis of M31. For the subsamples of metal-poor and metal-rich GCs, we have found that the metal-rich GCs are more centrally concentrated than the metal-poor GCs, and both subsamples show strong rotation. For the subsamples of bright and faint GCs, it is found that the rotation for the faint GCs is stronger than that for the bright GCs. We have identified 56 GCs and GC candidates with X-ray detection. It is found that the majority of X-ray emitting GCs follow the disk rotation, and that the redder, more metal-rich, and brighter GCs are more likely to be detected as X-ray emitting GCs. We have derived a rotation curve of M31 using the GCs at |Y|<0.6kpc. We have estimated the dynamical mass of M31 using `Projected Mass Estimator(PME)' and `Tracer Mass Estimator(TME)'. We finally discuss the implication of these results and compare the kinematics of GCs with that of planetary nebulae in M31.Comment: 62 pages, 26 figues, Accepted by Ap

Exploring Halo Substructure with Giant Stars. VI. Extended Distributions of Giant Stars Around the Carina Dwarf Spheroidal Galaxy -- How Reliable Are They?

The question of the existence of active tidal disruption around various dSph galaxies remains controversial. That debate often centers on the nature (bound vs. unbound) of extended populations of stars. However, the more fundamental issue of the very existence of the extended populations is still contentious. We present an evaluation of the debate centering on one particular dSph, Carina, for which claims both for and against the existence of stars beyond the King radius have been made. Our review includes an examination of all previous studies bearing on the Carina radial profile and shows that the survey method which achieves the highest detected dSph signal-to-background in the outer parts of the galaxy is the Washington M, T2 + DDO51 (MTD) filter approach from Paper II in this series. We then address statistical methods used to evaluate the reliability of MTD surveys in the presence of photometric errors and for which a new, a posteriori statistical analysis methodology is provided. Finally, these statistical methods are tested by new spectroscopy of stars in the MTD-selected Carina candidate sample. Of 74 candidate giants with follow-up spectroscopy, the MTD technique identified 61 new Carina members, including 8 stars outside the King radius. From a sample of 29 stars not initially identified as candidate Carina giants but that lie just outside of our selection criteria, 12 have radial velocities consistent with membership, including 5 extratidal stars. Carina is shown to have an extended population of giant stars extending to a major axis radius of 40' (1.44x the nominal King radius).Comment: 56 pages, 10 figures. Submitted to the Astronomical Journal, 2004 Sep 2

Lower Levels of Cervicovaginal Tryptophan are Associated with Natural Clearance of Chlamydia in Women

Chlamydiatrachomatis (Ct) infection causes significant morbidity. In vitro studies demonstrate that Ct growth inhibition occurs by interferon-gamma (IFN-γ)–mediated depletion of intracellular tryptophan, and some Ct strains utilize extracellular indole to restore tryptophan levels. Whether tryptophan levels are associated with Ct infection clearance in humans remains unknown. We evaluated tryptophan, indole, and IFN-γ levels in cervicovaginal lavages from women with either naturally cleared or persisting Ct infection. Women who cleared infection had significantly lower tryptophan levels and trended toward lower IFN-γ levels compared to women with persisting infection. Due to its volatility, indole was not measurable in either group

The Predominant CD4+ Th1 Cytokine Elicited to Chlamydia trachomatis Infection in Women Is Tumor Necrosis Factor Alpha and Not Interferon Gamma

Chlamydia trachomatis infection is the most prevalent bacterial sexually transmitted infection and can cause significant reproductive morbidity in women. There is insufficient knowledge of C. trachomatis-specific immune responses in humans, which could be important in guiding vaccine development efforts. In contrast, murine models have clearly demonstrated the essential role of T helper type 1 (Th1) cells, especially interferon gamma (IFN-γ)-producing CD4+ T cells, in protective immunity to chlamydia. To determine the frequency and magnitude of Th1 cytokine responses elicited to C. trachomatis infection in humans, we stimulated peripheral blood mononuclear cells from 90 chlamydia-infected women with C. trachomatis elementary bodies, Pgp3, and major outer membrane protein and measured IFN-γ-, tumor necrosis factor alpha (TNF-α)-, and interleukin-2 (IL-2)-producing CD4+ and CD8+ T-cell responses using intracellular cytokine staining. The majority of chlamydia-infected women elicited CD4+ TNF-α responses, with frequency and magnitude varying significantly depending on the C. trachomatis antigen used. CD4+ IFN-γ and IL-2 responses occurred infrequently, as did production of any of the three cytokines by CD8+ T cells. About one-third of TNF-α-producing CD4+ T cells coproduced IFN-γ or IL-2. In summary, the predominant Th1 cytokine response elicited to C. trachomatis infection in women was a CD4+ TNF-α response, not CD4+ IFN-γ, and a subset of the CD4+ TNF-α-positive cells produced a second Th1 cytokine

Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al