Overview on the use of synthetic peptides in human immunodeficiency virus infection.
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Biomedical subjects
Publications and source records attributed to R Cauda.
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NK activity and cells with NK phenotype (CD16+) were studied in 21 patients with HIV infection. In particular 8 patients with full-blown AIDS, 6 with AIDS related complex (ARC), 7 asymptomatic seropositive for anti-HIV antibodies were evaluated. Six subjects seronegative for anti-HIV antibodies from groups at risk for HIV infection were evaluated as well. NK activity was significantly reduced in AIDS and ARC patients but normal in asymptomatic seropositive subjects and in seronegative subjects at risk. NK cells (CD16+) were normal in AIDS patients, and in asymptomatic seropositive subjects, increased in ARC patients and in the subjects at risk. No statistical correlation was evident between the NK activity and the number of CD16+ cells in individual patients. The percentage of CD16+ cells coexpressing the HLA-DR marker i.e. CD16+ HLADR+ cells was significantly elevated only in ARC patients, and normal in the others. NK activity is the first line of defense against an invading virus and plays an important role in the immune surveillance of neoplasms. Therefore the reduced NK activity in AIDS and ARC patients can be consistent with the development of viral infections and unusual neoplasms frequently observed in such patients. The lack of correlation between defective NK activity and normal or increased number of cells with NK phenotype seems to indicate the existence of a more profound alteration in the function of NK cells rather than a simple numeric variation.
We sought to identify imbalances of immune regulatory cells that might contribute to the depression of cell-mediated immunity that occurs during an episode of herpes zoster. Peripheral blood mononuclear cells (PBMC) were obtained from patients with herpes zoster during the acute (less than 7 days after disease onset) and convalescent (more than 10 days after disease onset) phases of illness and from healthy seropositive donors. The PBMC were analyzed for: lymphoproliferative responses to varicella-zoster virus (VZV) antigens, Leu-3 (helper/inducer):Leu-2 (cytotoxic/suppressor) ratios, and percentages of suppressor cells as defined by coexpression of the Leu-2 and OKM1 antigens. Significantly depressed proliferative responses of VZV antigens and Leu-3:Leu-2 ratios, and increased percentages of Leu-2+ OKM1+ suppressor cells were observed in PBMC of acute phase herpes zoster patients as compared with the PBMC of convalescent patients or healthy donors. These differences were also observed in individual patients sequentially studied during both phases of disease. Cryopreserved acute phase PBMC suppressed the proliferative response of autologous convalescent phase PBMC to VZV antigens, but not to herpes simplex virus (HSV) antigens. The acute phase PBMC suppressor cell was radiation sensitive and was identified as a Leu-2+ cell by fluorescence-activated cell sorting. Thus, depression of cell-mediated immunity during the acute phase of herpes zoster was associated with a relative increase of lymphocytes expressing a suppressor cell phenotype and the activation of a radiosensitive Leu-2+ suppressor cell with some degree of antigen specificity.
Immunological studies on 29 children with congenital cytomegalovirus (CMV) infection were performed. Two groups of patients were considered according to the presence or absence of clinical symptoms. Asymptomatic patients had increased numbers of natural killer (NK) cells (CD 16+), activated NK cells (CD16+/HLA-DR+), and activated suppressor/cytotoxic cells (CD8+/HLA-DR+/TAC+). In addition, cells from this group of patients showed increased NK activity against fibroblasts infected with CMV and a significant proliferative response to CMV antigens. In contrast, cells from symptomatic patients had reduced NK activity against fibroblasts infected with CMV and a defective proliferative response to CMV antigens. In both groups, the number of total T, T-helper, and T-suppressor/cytotoxic cells was normal, as was the ratio of helper/suppressor. The reported differences in the immunological parameters between the asymptomatic and symptomatic patients suggest that cell-mediated immunity may play an important role in determining the outcome of the infection.
Condyloma acuminatum, CA or genital warts, are benign fibro-epithelial tumors with a predilection for moist environments, especially mucosal surfaces. This sexually transmitted disease (STD) is increasing rapidly in incidence. The lesions are associated with a number of human papillomavirus (HPV) types. Some HPV types are closely linked with genital (especially cervical) dysplasia and neoplasia. Treatment consists of such traditional modalities as podophyllin, cryotherapy or surgical excision and, more recently, administration of interferon (IFN).
Peripheral blood mononuclear cells were obtained from 20 untreated condyloma acuminatum patients and from an equal number of sex- and age-matched controls and assayed for cell surface antigen expression, natural killer activity, and lymphokine production. Patient peripheral blood mononuclear cells had significantly lower helper-to-suppressor T-cell ratios (Leu3/Leu2) (P less than 0.05) and significantly higher percentages of Leu 2+ Tac+ cells (activated suppressor/cytotoxic cells) (P less than 0.05) and Leu 2+ OKM1+ cells (suppressor cells) (P less than 0.01). Natural killer activity of condyloma acuminatum patients was significantly lower (P less than 0.05) than that of controls. Production of interleukin-2 and interferon gamma, but not interferon alpha, was significantly (P less than 0.01) decreased in condyloma acuminatum patients. There was an inverse correlation between the in vitro production of interleukin-2 and interferon gamma and the percentage of Leu 2+ OKM1+ cells (suppressor) (P less than 0.01). Thus, patients with condyloma acuminatum differ from controls by demonstrating decreased natural killer-cell activity, decreased production of lymphokines which enhance natural killer-cell activity (i.e., interferon gamma and interleukin-2), and an increased proportion of T cells with a suppressor phenotype.
Samples of peripheral blood lymphocytes (PBMC) were serially obtained from 30 patients with herpes zoster (HZ) and 10 patients with chickenpox (CP). Cells were assayed for NK-cell function and for the expression of surface membrane antigens which identify T-cell and NK-cell subsets. During the acute phase of disease (less than 7 days from onset), PBMC from patients with HZ had low proportions of T-helper (CD 4+) cells and a large number of T-suppressor (CD 8+) cells, resulting in a low T-helper/T-suppressor ratio. There was an increased percentage of nonspecific suppressor cells (GD 8+-CD 11+ cells) and increased expression of HLA-DR determinants on both CD 8+ and CD 4+ cells. The NK activity was depressed with no concomitant decrease in NK cells (CD 16+ or Leu 7+ cells). In the early convalescing phase of disease (8-14 days), there was a significant increase in CD 16+ cells and increased expression of HLA-DR on these cells, correlating with increased NK activity. In the late recovery phase (greater than 14 days), NK activity and levels of T-cell subpopulations were normal with the exception of increased CD 4+ cells and, consequently, of the helper/suppressor ratios. In the acute phase of CP (less than 7 days), the T-cell imbalances were similar to those encountered with HZ patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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Anti-Ia reactivity in sera from patients with chronic active hepatitis (CAH) were characterized by determining cross-reacting specificities with the antigen defined by anti-Ia monoclonal antibody (MoAb) and by studying the effect of CAH sera on the autologous mixed leukocyte reaction (MLR). Preincubation with autoimmune CAH sera lowered the percentage of Ia+ non-T cells stained by anti-Ia MoAb. HBsAg+ve/HBeAg+ve sera did not exert any blocking activity while 4 out of 11 HBsAg+ve/anti-HBe+ve sera exerted a significant blocking effect. Preincubation of cells with normal human serum (NHS) plus aggregated IgG did not block the binding of MoAb anti-Ia. Sera from patients with autoimmune or HBsAg+ve/anti-HBe+ve CAH, that blocked the binding of anti-Ia MoAb to Ia positive target cells by more than 20%, clearly inhibited the autologous mixed lymphocyte reaction (MLR). Both IgG and IgM fractions obtained by affinity chromatography from CAH sera inhibited the autologous MLR and blocked the binding of anti-Ia antibody to Ia positive target cells. A significant positive correlation (p less than 0.001) between serum anti-Ia reactivity and serum liver membrane antibodies (LMA) was observed. In 4 "autoimmune" CAH patients, steroid treatment induced a dramatic decrease in the anti-Ia reactivity.
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Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of 51Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a+ Leu-4- granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar to those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of 51Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.
This report provides evidence for the replication of varicella zoster virus (VZV) in Raji cells. Infection was achieved by co-cultivation of Raji cells with VZV-infected human fibroblasts. Replication of VZV, as assessed by immunofluorescence using monoclonal antibodies against VZV-glycoproteins, ranged from 18 to 24% of the cells. Electron microscopy detected complete virions within the membrane-bound cytoplasmic vesicles and free viral particles in the nuclear matrix as late as 12 days post-infection. Western blot analysis of infected Raji cells demonstrated VZV-specific glycoproteins. The availability of a VZV-susceptible cell line growing in suspension culture provides a useful model for future studies.
We evaluated the presence of CIC in 32 patients with histological proven cancer of endometrium: 23 stage IA or IB (i.e. localized disease), 9 in stage II or III (i.e. advanced disease). The determination of CIC was done at the time of the diagnosis before the patients underwent any surgical or medical therapy. The presence of CIC was demonstrated in 17% (4/23) of the patients with localized disease and in 56% (9/9) of the patients with more advanced disease. Our findings indicate that the presence of CIC is higher in patients with advanced endometrial carcinoma (stage II, III), than in those suffering of a more limited disease (stage IA, IB) and this seems could be consistent with a possible role in modulating the immune response against tumour itself.
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During acute viral hepatitis, we observed a significant decrease in OKT4/OKT8 ratio with a significant increase in the OKT8 positive subset in acute type B and non-A-non-B hepatitis. This altered ratio persisted in type B for a long time until HBsAg antibody became detectable, while it soon returned to normal in type A and non-A-non-B hepatitis. In the majority of acute hepatitis the altered ratio is because of an increase and not to a decrease in the whole T cell population, as described in chronic HBV infection. The number of HNK-1 positive cells remained raised during the recovery phase of type B and non-A-non-B hepatitis, a finding consistent with the hypothesis that NK cells play a role in the host defence against B and non-A-non-B virus infections. Serum beta 2-microglobulin concentrations were increased only in acute hepatitis B and non-A-non-B where immunological mechanisms are suspected to be involved, and showed a good correlation with the population of activated OKIa positive cells.
Type A, type B and type non-A, non-B hepatitis patients were followed up. Several parameters were checked at ten day intervals. Circulating immune complexes (CIC) were detected in a large percentage of patients by using the PEG test and an assay that makes use of bovine conglutinin (K) as recognition unit, and an enzymatically labelled immune complex as the probe. The decrease in the mean level of CIC in the patients correlated with the decrease in serum transaminases and bilirubinaemia in type A and type B hepatitis. Although the pattern of the mean values of the two assays was similar for type A and type B hepatitis, when the two CIC assays were compared for each patient, no significant correlation was found. In light of these and previous results, the necessity for performing CIC monitoring with more than one assay is also discussed.
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