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  • 1
    Keywords: CANCER ; CELLS ; IN-VITRO ; BLOOD ; human ; DISEASE ; POPULATION ; PROTEIN ; PATIENT ; RESPONSES ; DNA ; IFN-GAMMA ; INDUCTION ; ANTIGEN ; ANTIGENS ; T cells ; T-CELLS ; E7 ; papillomavirus ; IMMUNE-RESPONSES ; virus ; STAGE ; LESIONS ; NUMBER ; WOMEN ; cervical cancer ; cervical intraepithelial neoplasia ; CERVICAL-CANCER ; LYMPHOCYTES ; human papillomavirus ; HPV ; E6 ; HUMAN-PAPILLOMAVIRUS ; CANCER-PATIENTS ; IMMUNE-RESPONSE ; intraepithelial neoplasia ; human papilloma virus ; glutathione-S-transferase ; INVITRO ; IMMUNIZATION ; GRADE ; PERSISTENCE ; CD8(+) T cell ; CD4(+) T cell ; HPV16 E7
    Abstract: It has been suggested that local invasive procedures may alter the natural course of (pre)malignant cervical disease. This could be due to partial excision of the lesions, or via induction of cellular immunity against human papillomavirus (HPV) by the local invasive procedures. We studied the influence of local invasive procedures on HPV-16 E7 specific immune responses in patients with different grades of cervical intra-epithelial neoplasia (CIN) and different stages of cervical cancer. Blood was obtained at intake and after invasive procedures from patients with CIN or cervical cancer. Antigen specific T-cell responses were measured by IFN-gamma ELISPOT analysis, after stimulation with recombinant HPV-16 E7 protein. As expected, HPV-16 E7 specific IFN-gamma T cell responses were more frequent in HPV-16 DNA positive patients compared with that in HPV-16 DNA negative patients (39/50 vs. 16136, (p = 0.006, x(2) test). After invasive procedures, a small number of HPV-16 DNA positive CIN patients, but a considerable proportion of HPV-16 DNA positive cervical cancer patients, showed an enhancement of T cell responses against HPV-16 E7. Induction of T cell reactivity was most pronounced in cervical cancer patients who had undergone previous invasive procedures. Both CD4(+) and CD8(+) T cells showed E7 specific IFN-gamma production upon in-vitro stimulation. Our study shows that invasive procedures may enhance HPV-specific cell-mediated immunity in a considerable number of patients with cervical cancer, but in only a minority of CIN patients. Our data indicate that invasive procedures should be considered as possible confounding factors when analyzing the effectiveness of therapeutic immunization studies, especially, when induction of HPV-specific immune responses is used as intermediate end-point. (c) 2005 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 16353143
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  • 2
    ISSN: 1432-0584
    Keywords: Tγ Lymphocytosis ; Morphology ; Immunology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have studied the morphology and cytochemistry in relation to the immunological phenotyping and functional properties of T cells from eight patients with chronic Tγ lymphocytosis. At the light microscopic level the morphology of the patients' lymphocytes was similar to that described for large granular lymphocytes. Ultrastructurally, a division into two groups could be made on differences in the amount of cytoplasm and the location and the more irregular form of the nuclei. The lymphocytes of one group (five patients) had in common the phenotype Fcγ+, T3+, T4−, T8+, Ia−, M1− and demonstrated (with the exception of one patient) the same functions: presence of K-cell activity, absence of NK, helper and suppressor cell activities. In the other group (three patients), the lymphocytes of one patient showed the same phenotype and functions as those indicated above. The other two patients both lacked the T8 antigen on their lymphocytes but were different with regard to other surface markers. In addition, their cells were functionally identical: both demonstrated NK- and K-cell activity. Thus in this group of eight patients with chronic Tγ lymphocytosis, the immunological and functional subdivision paralleled in part a morphological division at the ultrastructural level.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1600-0765
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: To explore aspects of cellular immune responses in the pathogenesis of periodontitis we analyzed phenotype and function of peripheral T cells. Two groups of subjects participated: one group consisted of 10 highly susceptible patients with severe periodontitis (mean age 29 years) and a control group consisted of 10 age, gender and race matched subjects with gingivitis. From all subjects peripheral blood was collected. The results showed that the numbers of CD3+, CD4+ and CD8+ T cells as well as the CD4/CD8 ratio, and the proliferative capacity of T cells, were not different between the two groups of subjects. Also, proportions of naive and memory T cells for both the CD4+ and CD8+ subpopulations were not different. Functional heterogeneity within the CD4+ and CD8+ T cell compartments was determined by intracellular analysis of interferon-γ(IFN-γ) and interleukin-4 (IL-4) production. On the basis of these latter analyses among CD4+ and CD8+ cells, T helper (Th) 1 or Th2 function and T cytotoxic (Tc) 1 or Tc2 function, respectively, could be deduced. No significant differences in proportions of CD4+ and CD8+ T cells positive for intracellular IFN-γ or IL-4 were observed between periodontitis patients and gingivitis controls; however a higher level of intracellular IL-4 in CD8+ T cells was seen in periodontitis patients. This might indicate that there is a shift towards a Tc2 function within the CD8+ T cell subpopulation. The current explorative study suggests that further research into the role of CD8+T cells in the pathogenesis of periodontitis is warranted.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have produced five monoclonal antibodies (MoAb) directed against idiotypic determinants of surface immunoglobulins (sIg) expressed on malignant B cells from a patient suffering from prolymphatic leukaemia (B-PLL). The anti-idiotype MoAb were characterized by immunofluorescence-binding studies, allotype reactivity, and immunoprecipitation studies and were found to recognize at least two distinct epitopes on the sIg of the neoplastic B cells. Differential effects of the soluble anti-idiotype MoAb on phorbol myristate acetate (PMA)-induced B-PLL-cell proliferation were found: three types of anti-idiotype MoAb could be distinguished: (1) MoAb that enhanced the PMA-induced B-PLL-cell proliferation, (2) MoAb without effect, and (3) MoAb that inhibited the PMA-induced B-PLL-cell proliferation. Addition of the calcium ionophore A23187 could abolish the differential effects of the anti-idiotype MoAb on PMA-induced B-PLL-cell proliferation. The negative effect of the type 3 MoAb on PMA-induced B-PLL-cell proliferation was associated with a more than 10-fold stronger binding to sIg expressed on the B-PLL cells, compared with the other anti-idiotype MoAb. The differential effects of the types 1 and 2 MoAb cannot be explained solely by differences in the Fc portion of the MoAb and binding characteristics. Neither did differences in epitope specificity necessarily lead to differential effects on PMA-induced B-PLL-cell proliferation. In contrast to the clear differences found in the proliferation induction experiments, all MoAb were equally able to induce an early rise in free intracellular Ca2+ concentration. Our data suggest that for B-cell proliferation to occur, apart from early rises of intracellular Ca2+, more prolonged [Ca2+]i elevations or additional intracellular activation signals are required. The differences in proliferative responses of B-PLL cells to anti-idiotype MoAb may be relevant for immunotherapy of B-cell tumours with anti-idiotype MoAb.
    Type of Medium: Electronic Resource
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