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Lantz O.,Clinical Immunology Laboratory | Lantz O.,French Institute of Health and Medical Research
Cancer Research | Year: 2014

CD4+ T cells influence tumor immunity in complex ways that are not fully understood. In this study, we characterized a population of human differentiated effector CD4+ T cells that is defined by low levels of the interleukin (IL)-2 and IL-7 receptors (CD25-CD127-). We found that this cell population expands in patients with various types of cancer, including breast cancer, to represent 2% to 20% of total CD4+ blood T lymphocytes as compared with only 0.2% to 2% in healthy individuals. Notably, these CD25-CD127-CD4 T cells expressed effector markers such as CD244 and CD11b with low levels of CD27, contrasting with the memory phenotype dominating this population in healthy individuals. These cells did not cycle in patients, nor did they secrete IL-10 or IL-17, but instead displayed cytotoxic features. Moreover, they encompassed oligoclonal expansions paralleling an expansion of effectorCD8+ T cells that included tumor antigen-specific T cells.During neoadjuvant chemotherapy in patients with breast cancer, we found that the increase in CD25-CD127- CD4+ T cells correlated with tumor regression. This observation suggested that CD4+ T cells included tumor antigen-specific cells, whichmay be generated by or participate in tumor regressions during chemotherapy. In summary, our results lend support to the hypothesis that CD4+ T cells are involved in human antitumor responses. © 2014 American Association for Cancer Research.


Zhang G.,Clinical Immunology Laboratory | Li S.,Soochow University of China | Zhang X.,Soochow University of China | Hou J.,Soochow University of China
Journal of Urology | Year: 2011

Purpose We determined the soluble B7-H3 level and its clinical significance in serum and expressed prostatic secretions of patients with chronic prostatitis, including chronic bacterial prostatitis (type II) and chronic pelvic pain syndrome. Materials and Methods Using enzyme-linked immunosorbent assay we measured soluble B7-H3 in 11 patients with chronic prostatitis (type II), and 26 with inflammatory (type IIIA) and 54 with noninflammatory (type IIIB) chronic pelvic pain syndrome, and healthy donors. We assessed differences between these groups using Student's t test. As determined by the National Institutes of Health-Chronic Prostatitis Symptom Index, we correlated soluble B7-H3 with clinical pain using the Pearson test. Results We found no significant difference between serum soluble B7-H3 in healthy donors and patients with chronic prostatitis (p = 0.897). However, soluble B7-H3 in expressed prostatic secretions was statistically significantly decreased in patients with chronic prostatitis vs controls (p <0.001). ROC using soluble B7-H3 greater than 38.82 ng/ml in expressed prostatic secretions distinguished patients with chronic prostatitis from healthy donors with 90.9% sensitivity and 83.5% specificity. Also, soluble B7-H3 levels in expressed prostatic secretions correlated negatively with the Chronic Prostatitis Symptom Index and the pain subscore. Compared to the pretreatment level soluble B7-H3 in expressed prostatic secretions was significantly increased in patients with a greater than 25% decrease in the Chronic Prostatitis Symptom Index total score (p = 0.016). Conclusions Data indicate that the soluble B7-H3 level in expressed prostatic secretions is a novel chronic prostatitis marker that correlates negatively with subjective symptoms. © 2011 American Urological Association Education and Research, Inc.


Schmidt C.,International AIDS Vaccine Initiative IAVI | Jaoko W.,University of Nairobi | Omosa-Manyonyi G.,University of Nairobi | Kaleebu P.,UVRI IAVI HIV Vaccine Program | And 17 more authors.
Human Vaccines and Immunotherapeutics | Year: 2014

Long-term safety is critical for the development and later use of a vaccine to prevent HIV/AIDS. Likewise, the persistence of vaccine-induced antibodies and their impact on HIV testing must be established. IAVI has sponsored several Phase I and IIA HIV vaccine trials enrolling healthy, HIV-seronegative African volunteers. Plasmid DNA and viral vector based vaccines were tested. No vaccine-related serious adverse events were reported. After completion of vaccine trials conducted between 2001-2007, both vaccine and placebo recipients were offered enrolment into an observational long-term follow-up study (LTFU) to monitor potential late health effects and persistence of immune responses. At scheduled 6-monthly clinic visits, a health questionnaire was administered; clinical events were recorded and graded for severity. Blood was drawn for HIV testing and cellular immune assays. 287 volunteers were enrolled; total follow-up after last vaccination was 1463 person years (median: 5.2 years). Ninety-three (93)% of volunteers reported good health at their last LTFU visit. Infectious diseases and injuries accounted for almost 50% of the 175 reported clinical events, of which over 95% were mild or moderate in severity. There were 30 six pregnancies, six incident HIV infections and 14 volunteers reported cases of social harm. Persistence of immune responses was rare. No safety signal was identified. No potentially vaccine-related medical condition, no immune mediated disease, or malignancy was reported. HIV vaccines studied in these trials had a low potential of induction of persisting HIV antibodies. © 2014 Landes Bioscience.


PubMed | Clinical Immunology Laboratory, Projet San Francisco PSF ; Kigali, University of Limpopo, Zambia Emory HIV Research Program ZEHRP and 7 more.
Type: Journal Article | Journal: Human vaccines & immunotherapeutics | Year: 2014

Long-term safety is critical for the development and later use of a vaccine to prevent HIV/AIDS. Likewise, the persistence of vaccine-induced antibodies and their impact on HIV testing must be established. IAVI has sponsored several Phase I and IIA HIV vaccine trials enrolling healthy, HIV-seronegative African volunteers. Plasmid DNA and viral vector based vaccines were tested. No vaccine-related serious adverse events were reported. After completion of vaccine trials conducted between 2001-2007, both vaccine and placebo recipients were offered enrolment into an observational long-term follow-up study (LTFU) to monitor potential late health effects and persistence of immune responses. At scheduled 6-monthly clinic visits, a health questionnaire was administered; clinical events were recorded and graded for severity. Blood was drawn for HIV testing and cellular immune assays. 287 volunteers were enrolled; total follow-up after last vaccination was 1463 person years (median: 5.2 years). Ninety-three (93)% of volunteers reported good health at their last LTFU visit. Infectious diseases and injuries accounted for almost 50% of the 175 reported clinical events, of which over 95% were mild or moderate in severity. There were 30 six pregnancies, six incident HIV infections and 14 volunteers reported cases of social harm. Persistence of immune responses was rare. No safety signal was identified. No potentially vaccine-related medical condition, no immune mediated disease, or malignancy was reported. HIV vaccines studied in these trials had a low potential of induction of persisting HIV antibodies.


Cicero M.F.,Federal University of São Paulo | Pena N.M.,Federal University of São Paulo | Santana L.C.,Federal University of São Paulo | Arnold R.,Federal University of São Paulo | And 5 more authors.
BMC Infectious Diseases | Year: 2016

Background: The Hepatitis Delta Virus (HDV) can increase the incidence of fulminant hepatitis. For this infection occurs, the host must also be infected with Hepatitis B Virus. Previous studies demonstrated the endemicity and near exclusivity of this infection in the Amazon region, and as a consequence of the difficulty in accessing this area we used dried blood spots (DBS) in sample collection. The aims of this study were to investigate the presence of recombination, to analyze the epidemiology, ancestry and evolutionary pressures on HDV in Brazil. Methods: Blood samples from 50 individuals were collected using dried-blood spots (DBS 903, Whatman), and sent via regular mail to Retrovirology Laboratory from Federal University of São Paulo, where the samples were processed. In the analysis the following software were used: PhyML, RDP, BEAST, jModelTest and CODEML. Results: Our results confirm the prevalence of HDV-3 in the Amazon region of Brazil, with the absence of inter-genotypic recombination. It was identified a positive selection in probable epitopes of HDV on B lymphocytes that might indicate that the virus is changing to escape the humoral response of the host. The analysis of the time of the most common ancestor demonstrated the exponential growth of this virus in late 1970s that lasted until 1995, after which it remained constant. It was also observed a probable founder effect in two cities, which demonstrate the need to focus on prevention methods against HBV/HDV infection. Conclusion: We confirmed the prevalence of HDV-3 in the Amazon region of Brazil, without inter-genotypic recombination. The analysis of the time of the most common ancestor showed that this infection remain constant in the studied area. Taking into account the probable founder effect established in the cities of Rio Branco and Porto Velho, a focus on preventive methods is recommended against these infections. © 2016 The Author(s).

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