BackgroundCD4+/CD8+ double positive (DP) T cells have been described in healthy individuals as well as in patients with autoimmune and chronic infectious diseases. In chronic viral infections, this cell subset has effector memory phenotype and displays antigen specificity. No previous studies of double positive T cells in parasite infections have been carried out.Methodology/Principal FindingsSeventeen chronic chagasic patients (7 asymptomatic and 10 symptomatic) and 24 non-infected donors, including 12 healthy and 12 with non-chagasic cardiomyopathy donors were analyzed. Peripheral blood was stained for CD3, CD4, CD8, HLA-DR and CD38, and lymphocytes for intracellular perforin. Antigen specificity was assessed using HLA*A2 tetramers loaded with T. cruzi K1 or influenza virus epitopes. Surface expression of CD107 and intracellular IFN-γ production were determined in K1-specific DP T cells from 11 chagasic donors. Heart tissue from a chronic chagasic patient was stained for both CD8 and CD4 by immunochemistry. Chagasic patients showed higher frequencies of DP T cells (2.1%±0.9) compared with healthy (1.1%±0.5) and non-chagasic cardiomyopathy (1.2%±0.4) donors. DP T cells from Chagasic patients also expressed more HLA-DR, CD38 and perforin and had higher frequencies of T. cruzi K1-specific cells. IFN-γ production in K1-specific cells was higher in asymptomatic patients after polyclonal stimulation, while these cells tended to degranulate more in symptomatic donors. Immunochemistry revealed that double positive T cells infiltrate the cardiac tissue of a chagasic donor.ConclusionsChagasic patients have higher percentages of circulating double positive T cells expressing activation markers, potential effector molecules and greater class I antigenic specificity against T. cruzi. Although K1 tetramer positive DP T cell produced little IFN-γ, they displayed degranulation activity that was increased in symptomatic patients. Moreover, K1-specific DP T cells can migrate to the heart tissue.
Human papillomavirus seropositivity is associated with measures of sexual behavior, particularly a greater lifetime number of sexual partners. Hormonal and tobacco/cigarette use may be factors influencing the HPV seropositivity in women older than 45 years old.
A variety of immunological methods have proven useful for Paracoccidioidomycosis (PCM) diagnosis; however, they are often time consuming and many lack sensitivity and specificity, partially attributed to the use of crude antigens, which give cross reactivity. Until now, attempts to clone and express Paracoccidioides brasiliensis immunodominant antigens have presented difficulties of process and problems of cost. In an attempt to obtain a more rapid, sensitive, and specific test for PCM diagnosis, we subcloned the P. brasiliensis p27 gene and used the recombinant protein as the antigen in dot blot assays to evaluate its usefulness in paracoccidioidomicosis diagnosis. The development of an optimised procedure for p27 recombinant protein purification and production led to an easier and less expensive process than the one previously used in our laboratory and allowed the availability of enough purified protein for its evaluation as the antigen in the dot blot assays. In these assays, antibodies present in ten serum samples from seven patients with PCM recognised the recombinant protein showing a sensitivity of 100% with a specificity of 98%. These results confirm the value of the 27-kDa recombinant antigen in the serodiagnosis of paracoccidioidomycosis and that the dot blot format is an alternative to the immunoenzymatic assay procedure.
Only a small proportion of women infected with Human Papillomavirus (HPV) develop cervical cancer. Host immune response seems to play a role eliminating the viral infection and preventing progression to cancer. Characterization of tumor infiltrating lymphocytes (TILs) in cervical pre-neoplastic lesions and cervical cancer may be helpful to understand the mechanisms that mediate this protection. The aim of this study was to determine if there are differences in the localization and density (cells/mm 2 ) of CD8+ T-cells, CD4+ T-cells and Tregs (CD25 + Foxp3+) in cervical pre-neoplastic lesions and cervical cancer. Immunohistochemical analysis of sections of 96 (26 CIN1, 21 CIN2, 25 CIN3, and 24 SCC) samples revealed that regardless of CIN grades, CD8+ T-cells are more abundant than CD4+, CD25+ and Foxp3+ cells in both the stroma and epithelium. There was a higher density of CD8+ cells in the stroma of cervical cancer compared to CIN3 (OR 0 4.20, 95% CI 1.2-15), CIN2 (OR 0 7.86, 95% CI 1.7-36.4) and CIN1 (OR 0 4.25, 95% CI 1.1-17). Studies evaluating whether these cells are recruited before or after cancer progression will be helpful to understand the role of these cells in the natural history of HPV-induced lesions.
In the context of opportunistic cervical cancer screening settings of low‐and‐middle‐income countries, little is known about the benefits of high‐risk human papillomavirus (hrHPV) testing on high‐grade cervical abnormality detection among women with atypical squamous cells of undetermined significance (ASC‐US) cytology in routine clinical practice. We compared the effectiveness of immediate colposcopy (IC), conventional cytology at 6 and 12 months (colposcopy if ≥ASC‐US) (RC) and hrHPV testing (colposcopy if hrHPV‐positive) (HPV) to detect cervical intraepithelial neoplasia grade 2 or more severe diagnoses (CIN2+) among women aged 20 to 69 years with ASC‐US in routine care. Participants (n = 2661) were evenly randomized into three arms (n = 882 IC, n = 890 RC, n = 889 HPV) to receive services by routine healthcare providers and invited to an exit visit 24 months after recruitment. Histopathology was blindly reviewed by a quality‐control external panel (QC). The primary endpoint was the first QC‐diagnosed CIN2+ or CIN3+ detected during three periods: enrolment (≤6 months for IC and HPV, ≤12 months for RC), follow‐up (between enrolment and exit visit) and exit visit. The trial is completed. Colposcopy was done on 88%, 42% and 52% of participants in IC, RC and HPV. Overall, 212 CIN2+ and 52 CIN3+ cases were diagnosed. No differences were observed for CIN2+ detection (P = .821). However, compared to IC, only HPV significantly reduced CIN3+ cases that providers were unable to detect during the 2‐year routine follow‐up (relative proportion 0.35, 95% CI 0.09‐0.87). In this context, hrHPV testing was the most effective and efficient management strategy for women with ASC‐US cytology.
There is lack of age-specific seroprevalence surveys and identification of factors associated with herpes simplex virus type-2 seropositivity (HSV-2) in rural populations in Colombia. A random sample of 869 women was interviewed about socio-demographic aspects, sexual and reproductive history. Antibodies to HSV-2 were determined by a specific type immunoenzymatic technique (ELISA). Participants had a mean age of 38±16.1 years, 67% were married, 60% monogamous and 47% reported use of condoms. HSV-2 seroprevalence was 19.1% (95% CI: 16.6-21.9) and it was strongly associated with increasing age (Ptrend<0.001). In the logistic regression analysis, women who reported between two or three lifetime sexual partners (OR=2.4; 95% CI: 1.5-3.7), >31 years of sexual activity with regular or occasional sexual partners (OR=4.3; 95% CI: 1.2-15.7) and not using condoms with regular sexual partners (OR=2.1; 95% CI: 1.4-3.3) were more likely to be HSV-2 seropositive. The overall seroprevalence rate of women of Pueblorrico, Colombia, is lower than that reported in other Latin American countries especially in women>45 years. The difference may be explained by higher prevalence of condom use in this population or lower exposure to herpes infection in male as well as females in the past.
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