The major CD8 T cell effector memory subset in the normal and <it>Chlamydia trachomatis</it>-infected human endocervix is low in perforin

<p>Abstract</p> <p>Background</p> <p>The local tissue microenvironment plays an important role in the induction, homing, maintenance and development of effector functions of T cells. Thus, site-specific differences in phenotypes of mucosal and systemic T cell populations have been observed. <it>Chlamydia trachomatis</it> most commonly infects the endocervix in women, yet little is known about <it>Chlamydia</it>-specific effector T cell immunity at this unique mucosal site. Our previous flow-cytometry-based study of cervical-cytobrush retrieved cells indicated that CD8 T cells are significantly increased in the <it>C. trachomatis</it>-infected human endocervix. The cytolytic function of CD8 T cells is important in the protective immunity against many intracellular pathogens, and requires the cytolytic granule perforin to facilitate the entry of other molecules that mediate the lysis of target cells. Determination of perforin expression of the CD8 T cell population in the endocervix would therefore provide insights on the granule-mediated cytolytic potential of these cells at this site.</p> <p>Results</p> <p>Our histological data revealed that <it>C. trachomatis</it>-infected tissues have significantly higher numbers of CD3 and CD8 T cells compared to non-infected tissues (p<0.01), and that the majority of CD8⁺ cells do not express perforin <it>in situ</it>. A subsequent flow cytometric analysis of paired blood and endocervix-derived cells (n=16) revealed that while all the CD8 T cell subsets: naïve, effector memory (T_EM), central memory (T_CM) and terminally differentiated effector memory (T_EMRA) can be found in the blood, the endocervix is populated mainly by the T_EM CD8 T cell subset. Our data also showed that perforin expression in the T_EM population is significantly lower in the endocervix than in the blood of <it>C. trachomatis</it> positive women (n=15; p<0.0001), as well as in <it>C. trachomatis</it>-negative individuals (n=6; p<0.05). Interestingly, our <it>in vitro</it> co-culture study suggests that the exposure of HeLa 229 cervical epithelial cells to IFN gamma could potentially induce a decrease in perforin content in CD8 T_EM cells in the same microenvironment.</p> <p>Conclusions</p> <p>The low perforin content of CD8 T_EM cells in the endocervix, the local site of <it>C. trachomatis</it> infection in women, may reflect the unique immunological environment that balances immune protection against sexually transmitted infections and immune- tolerance to support conception.</p

Molecular evidence for allopolyploid speciation and a single origin of the western Mediterranean orchid Dactylorhiza insularis (Orchidaceae)

The hybrid origin of the western Mediterranean orchid Dactylorhiza insularis was demonstrated by genetic markers. Allozyme data showed that throughout its range I). insularis has an allotriploid constitution and reproduces apomictically. The parental species of D. insularis were identified as D. romana and D. sambucina; they contributed 2 alleles and 1 allele, respectively, at the allozyme loci studied. The maternal species of D. insularis was D. romana, as inferred from cpDNA (trnL(UAA) intron). High genetic similarities were found when comparing present populations of D. romana and D. sambucina with their respective genomes 'frozen' in D. insularis. Dactylorhiza insularis showed fixed (or nearly fixed) heterozygosity at 11 out of the 19 loci studied, and poor genetic variation: eight multilocus genotypes were detected at allozyme level. No multilocus genotype differs from the most similar one by more than one allele substitution. All D. insularis individuals showed the same cpDNA haplotype (I), regardless of their geographic origin and multilocus genotype. The I haplotype is similar, but not identical to that found in D. romana (R). No recurrent formation of D. insularis was observed in hybrid zones between D. romana and D. sambucina, where diploid sexual hybrids (F-1, F-n, backcrosses) were detected. Available data agree with a single origin for D. insularis, which possibly occurred in the present postglacial, when L). romana and D. sambucina, expanding from their glacial refugia, came into contact. The genetic homogeneity found between D. romana and D. markusii, both from their locus classicus, indicates that the latter is a junior synonym of D. romana; on the other hand, D. romana and D. sambucina are well differentiated species(D-Nei=0.59)

Predicting survival in newly diagnosed idiopathic pulmonary fibrosis: a 3-year prospective study.

The natural history of idiopathic pulmonary fibrosis (IPF) is not well defined and its clinical course is variable. We sought to investigate the survival and incidence of acute exacerbations (AEs) and their significant predictors in newly diagnosed patients. 70 patients newly diagnosed with IPF were prospectively followed for at least 3 yrs. Baseline evaluation included Medical Research Council dyspnoea score (MRCDS), 6-min walk test, pulmonary function tests, all of which were repeated at 6 months, and high-resolution computed tomography. A retrospective cohort of 68 patients was used for confirmation. Mean survival from the time of diagnosis was 30 months, with a 3-yr mortality of 46%. A Risk stratificatiOn ScorE (ROSE) based on MRCDS > 3, 6-min walking distance ≤ 72% predicted and composite physiologic index > 41 predicted 3-yr mortality with high specificity. 6-month progression of ROSE predicted rapid progression. 3-yr incidence of AE was 18.6%, mostly occurring in the first 18 months; risk factors for AE were concomitant emphysema and low diffusing coefficient of the lung for carbon monoxide. Results were confirmed in an independent cohort of patients. In newly diagnosed IPF, advanced disease at presentation, rapid progression and AEs are the determinants of 3-yr survival. The purpose of the multifactorial ROSE is to risk-stratify patients in order to predict survival and detect rapid disease progression

Riqualificazione area ex Mercati Generali, via Ostiense. Proposta preliminare di adeguamento del progetto

Riqualificazione area ex Mercati Generali, via Ostiense (Roma Capitale, Municipio VIII)-Proposta preliminare di adeguamento del progetto; Concedente: Roma Capitale, Dipartimento Programmazione e Attuazione Urbanistica, Direzione Trasformazione Urbana, U. O. Città Storica e Ambiti di Tutela e Riqualificazione; Concessionario: SVILUPPO CENTRO OSTIENSE S.r.l.; Retail Masterplanning Strategy: Chapman Taylor Architetti, Studio Internazionale Architettura|Urbanistica|Design; gruppo di ricerca per la proposta di progetto: Università degli Studi Roma Tre (Dipartimenti di: Architettura, Ingegneria, Giurisprudenza, Economia, Studi Aziendali); responsabili scientifici: S. Cordeschi, M. Furnari; componenti: A.C. Beuchat, C. Garofalo, E. Buffo, S. Orsi, L. Evangelisti, C. Gemma, F. Marchetti, S. Muccitelli, E. Paglialunga, P. Porretta, L. Solero, M.F. Talamonti, R. De Lieto Vollar