6 research outputs found
Epithelium-Free Area in The Thymic Cortex of Rats
The histology of epithelium-free areas in the subcapsular region of the thymus was
studied in Wistar rats. Lymphocytes in these areas were CD4/CD8 double-positive, TCR
α/β positive in low intensity, and in CD5 labeling either negative or positive in low
intensity. There was a high proliferative activity as assessed by bromodeoxyuridine
incorporation in vivo and detected by immunohistochemistry. Various macrophage
types were observed. They were either large and round to slightly dendritic, or small
and dendritic. Most large cells were positive for MHC Class II, and labeled by the
antimacrophage antibodies ED1 and ED2. A few cells were strongly positive for Sudan
black, Oil red O, nonspecific esterase, and acid phosphatase; they resembled the large
rounded macrophages in the corticomedullary zone, although their MHC Class II and
ED2 staining was more intense. A few cells showed features of tingible body
macrophages, as they contained cellular debris
Interferon Gamma Alters the Phenotype of Rat Thymic Epithelial Cells in Culture and Increases Interleukin-6 Production
Rat thymic epithelial cells (TEC) in long-term culture were characterized by
anticytokeratin monoclonal antibodies (mAbs) and electron microscopy. Phenotypic
analysis performed by a large panel of mAbs showed that the highest percentage of
these cells was of the subcapsular/medullary type.
Recombinant rat interferon (IFN)-gamma up-regulated class-I and class-II MHC
expression by TEC in culture as confirmed by immunohistochemistry and flow
cytometry, but did not significantly alter other cell markers. TEC supernatants of IFN-gamma-
treated cultures showed higher interleukin-6 (IL-6) activity, compared to the
control, as determined by proliferation of the IL-6-sensitive B9-cell line. Increased IL-6
activity was probably not a consequence of increased TEC number in IFN-gammatreated
cultures because IFN did not significantly stimulate TEC proliferation in vitro. In
contrast, IL-6 significantly stimulated TEC proliferation, indicating that this cytokine is
not only a regulatory molecule for T-cell proliferation, but could also be an autocrine
growth factor for thymic epithelium
Differential Effects of X-Irradiation and Cyclosporin-A Administration on the Thymus with Respect to the Generation of Cyclosporin-A-Induced Autoimmunity
Cyclosporin A (CsA), a potent inhibitor of T-cell activation, has been shown to have several
effects on thymocyte maturation, thymic stromal cells, and the generation of autoreactive T
cells. In Lewis rats, the combination of lethal irradiation, syngeneic bone marrow
transplantation, and a 4-week course of CsA administration causes the development of an
autoimmune disease (CsA-AI) resembling allogeneic graft-versus-host disease. This occurs
upon withdrawal of CsA, provided the thymus receives irradiation and is present during
CsA treatment. In this study, the separate effects of irradiation or CsA treatment on thymic
stromal cells and thymocytes, compared to the combinatory effects, were examined using
immunohistochemistry and tricolor flow cytometric analysis
Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study
BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC