B-cell help by Tc2 cells.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
F Aiuti
Publications and source records attributed to F Aiuti.
Apoptosis in asymptomatic HIV-1 seropositives immunized with HIV-1 env glycoprotein (gp160): effects of administration of Zidovudine in vivo and interleukin-2 in vitro.
In this paper we report the effects of VaxSyn (Protein Sciences Corp.) immunization on spontaneous apoptosis occurring in vitro after culture of PBMC in medium alone in 30 HIV-seropositive patients enrolled in a double-blind clinical trial that included three groups: treatment with VaxSyn, AZT and VaxSyn, and AZT. Our data show no significant modifications in the levels of apoptosis observed in the three groups over the long-term follow-up (up to 720 days). This was not associated with any significant modifications in other clinical or immunological features. However, analysis of apoptosis performed shortly after the first immunization (at days 3 and 7) showed a significant reduction in the rate of apoptosis in patients receiving AZT and AZT and VaxSyn, as compared with patients receiving VaxSyn alone (30.42 +/- 2.52 SE at day 0 and 23.74 +/- 1.84 at day 3; p = 0.039). Our data also indicate that addition of IL-2 in vitro had a significant inhibitory effect on mortality in all the randomization groups, especially in those receiving AZT (alone or in combination with VaxSyn).
Adult↗
The Italian quality control study for evaluation of CD4 cells in centres involved in the treatment of HIV-1 patients. Italian CD4 Quality Control Group.
We report on the experience of establishing a national network for a quality control programme in evaluating CD4 cell counts in most Italian centres involved in the care of patients with HIV disease. The 68 centres were divided according to their geographical location into eight groups, and twice a year (tests A and B) they received three coded whole blood samples (two were replicates of the same sample) obtained from two informed HIV+ patients, one with CD4 counts/mm3 expected to be < 200 and one with values > 300. The medians of the determinations performed by the labs involved in each of the eight areas were taken as the 'true' values for each sample. Unsatisfactory performances for percentage of CD4 cells were identified as a CD4 analysis with residual values > or = +/- 5% and with deviates > or = +/- 2. For absolute numbers of CD4 cells, an unsatisfactory performance was defined as CD4 counts with residual > +/- 100 CD4 cells/mm3 and with deviates > or = +/- 2. The residual value is the CD4 value reported by each lab minus the median value. The deviate is the residual divided by the modified interquartile range (IQR x 0.75). Most of the centres provided reliable results. However, some labs failed to provide satisfactory results for percentages (6.25% of the tested labs for test A and 6.17% for test B) or absolute numbers (16.25% test A and 12.34% test B). Only 3.7% of the labs gave unsatisfactory results in both tests. Four of the unsatisfactory results from the two tests gave an error in absolute numbers > +/- 200 CD4 cells/mm3. Our data suggest that most Italian labs provide reliable results in evaluating the numbers of CD4 cells in HIV-1+ samples, but the importance of running a quality control programme is highlighted by our experience with those centres which provide unsatisfactory data which may lead to incorrect classification of the patients or assessment of treatment.
CD4 Lymphocyte Count↗
C-C chemokines, IL-16, and soluble antiviral factor activity are increased in cloned T cells from subjects with long-term nonprogressive HIV infection.
A combination of three beta, or C-C, chemokines, as well as IL-16, have been shown to inhibit HIV replication in vitro. Cellular antiviral factor is a more potent agent, and acts on all HIV strains. All are mainly, but not exclusively, produced by CD8+ T cells, both in HIV+ and healthy subjects. We studied the production of these HIV-suppressive factors in patients with HIV infection at different stages of disease. No difference in production by PBMC stimulated with PHA has been observed in asymptomatic HIV+, long-term nonprogressors (LTnP), and AIDS patients. When T cell line supernatants from these three groups were studied, no significant difference was found for C-C chemokines or IL-16 production, and viral suppression. However, T cell clones from LTnP secreted higher levels of all three chemokines, IL-16, and exerted a stronger inhibition on HIV replication. CD8+ clones showed a higher production than CD4+ clones. These clones were able to produce all antiviral factors irrespective of the secretion of type 1 or type 2 cytokines. The antiviral activities were not correlated, implying that viral suppression did not depend solely on C-C chemokines or IL-16. We postulate that all factors are needed to prevent HIV disease progression.
Antiviral Agents↗
Italian multicentre study of didanosine compassionate use in advanced HIV infection. Italian BMS-906 Study Group.
The aim of the present study, a multicentre trial of didanosine (ddI) compassionate use, was to identify factors associated with a better outcome in patients given ddI monotherapy. Enrolled were 1047 HIV-positive patients intolerant of and/or unresponsive to zidovudine (ZDV) therapy, with CD4+ cell counts of < 200/microliter or AIDS. Didanosine was given at a dose of 250 mg b.i.d. (patients > or = 60 kg) or 167 mg b.i.d. (patients < 60 kg). Clinical examinations and laboratory tests were performed every two months. Endpoints included death, the occurrence of a new AIDS-defining disease, or permanent discontinuation of ddI for a severe adverse event. At entry, the median CD41 cell count was 47/microliter and the median duration of prior ZDV treatment 19 months; 446 patients (43%) were classified as having AIDS. Severe toxicity occurred in 143 subjects (14%); the frequency of pancreatitis was very low (0.2%). The benefit in terms of CD4+ cell counts was greater for patients whose counts exceeded 100/microliter at entry and remained at this level until month 12 in those patients still receiving treatment. Death and/or new AIDS-defining events were observed in 374 cases (36%) over a median follow-up of eight months. AIDS dementia was observed in 11 patients (1%). Multivariate analysis of survival without disease progression showed that the factors associated with a worse outcome include the severity of immunodepression, a diagnosis of AIDS at entry, and a history of both intolerance of and clinical resistance to ZDV. Surprisingly, the patients who had received previous prolonged treatment with ZDV had a better outcome. In conclusion, severely immunodepressed patients previously administered long-term monotherapy may receive a short-term benefit from being switched to another antiretroviral drug.
AIDS Dementia Complex↗
CD28 costimulation and T lymphocyte proliferative responses in HIV-1 infection.
To investigate whether defective costimulatory signals could be involved in the loss of T lymphocyte functions during HIV-1 infection, we tested the effect of CD28 costimulation on both T cell receptor/CD3 and HIV-1 antigen-induced proliferative responses. Although CD3-mediated responses significantly decreased with more advanced stages of HIV-1 infection, the ability of potentiating the responses through CD28 costimulation was maintained at all stages and did not differ from that of HIV-1- subjects. When CD28 costimulation was studied in lymphocyte cultures stimulated with HIV-1 gp160 or p24, potentiation was seen only when a significant response was present without additional CD28 triggering, namely in subjects receiving active immunization with recombinant gp160. These results confirm the integrity of the CD28 pathway of costimulation during HIV-1 infection, and suggest that lymphocytes responding to soluble HIV-1 antigen are not deleted in HIV-1-infected patients, but do not receive significant priming during the natural course of the infection.
CD28 Antigens↗
IL-10 production and CD40L expression in patients with common variable immunodeficiency.
The authors studied CD40 ligant (CD40L) expression and interleukin-10 (IL-10) production in 16 patients with common variable immunodeficiency (CVI). Mean CD40L expression, determined by using cytofluorimetry, and measured as the mean fluorescence intensity following stimulation of peripheral blood mononuclear cells (PBMC) with phorbol myristate acetate (PMA) and calcium ionophore in 12 patients, was comparable to that of controls. However, three CVI patients showed fluorescence intensity in stimulated cells below 2 standard deviations of normal donors' mean and two other patients had only a slight increase of stimulated versus unstimulated cells (< 10 channels). IL-10 production after stimulation of PBMC with both anti-CD3 or anti-CD3 plus PMA gave similar results in CVI patients and normal controls. In vitro stimulation of PBMC with anti-CD40 and various combinations of cytokines (IL-2, IL-4 and IL-10) induced IgG production above 100 ng/ml in one CVI patient out of 13 tested. The data suggest that alterations of IL-10 production are unlikely to play a major role in the pathogenesis of impaired IgG production in most CVI patients. CD40L appears to be normally expressed in two thirds of CVI patients, but it may be functionally defective.
Adolescent↗
Long-term evaluation of cellular immunity during antiretroviral therapy and immunization with human immunodeficiency virus type 1 (HIV-1) Env glycoprotein in HIV-1-infected persons.
Cellular immune responses to human immunodeficiency virus type 1 (HIV-1) antigens, microbial recall antigens, and CD3 monoclonal antibody were studied in HIV-1-infected asymptomatic patients in a phase II, double-blind trial of immunization with recombinant HIV-1 gp160 in or not in association with zidovudine. A vigorous and persistent lymphoproliferative response (LPR) to HIV-1 Env antigens was observed in vaccinated patients. Neither Env-specific lymphocyte cytotoxicity nor LPR to recall antigens was significantly influenced by gp160 administration. The induction of LPRs to HIV-1 envelope proteins did not show positive effects on the course of HIV-1 infection. Patients treated with zidovudine alone or in combination with the immunogen showed improvement of T lymphocyte responses and transient reduction of viremia. These results suggest that antiretroviral therapy is more beneficial than immunization with gp160 and should always be considered in association with future vaccination and immunotherapeutic interventions in HIV-1-infected subjects.
Adolescent↗
Antiretroviral therapy and HIV-related retinal microangiopathy.
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AIDS-Related Opportunistic Infections↗
Th2-type cytokines, hypereosinophilia, and interleukin-5 in HIV disease.
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Cytokines↗
Proliferative responses to PHA, anti-CD3 and antigens in patients with lymphoproliferative disease of granular lymphocytes. Mannoproteins of Candida albicans induce proliferation and cytotoxicity.
In this paper we investigated the lymphoproliferative and cytotoxic responses of peripheral blood mononuclear cells (PBMC) of patients affected with lymphoproliferative disease of granular lymphocytes of T cell origin to mitogens and antigens. Most patients with lymphoproliferative disease of granular lymphocytes (LDGL) showed a severely impaired PBMC proliferative capacity in response to phytohemagglutinin, anti-CD3 and tetanus toxoid, an impairment that, in the case of anti-CD3 response, appears to be related to a defect of phosphorylation in response to triggering. In contrast, at least 50% of the patients had normal proliferation in response to a mannoprotein fraction purified from Candida albicans. These data suggest that some CD3+ GL from LDGL patients, that usually respond poorly to proliferative stimuli in vitro, can be triggered to perform these functions by candidal antigens.
Adult↗
Eosinophil-derived proteins in postprandial (food-dependent) exercise-induced anaphylaxis.
BACKGROUND: Postprandial exercise-induced anaphylaxis (PPEIAn) is a form of EIAn in which the ingestion of food before the exercise is associated with the onset of symptoms. Skin reactivity and the presence of specific serum IgE to several food allergens suggest the occurrence of food-dependent allergic mechanisms. METHODS: In order to study the involvement of eosinophils in the pathogenesis of PPEIAn we measured the changes in serum eosinophil cationic protein (ECP) and eosinophil protein X/eosinophil-derived neurotoxin (EPX/EDN) levels in 6 patients with PPEIAn, subjected to three separate challenges with either suspected foods only, exercise after a meal without or with suspected food ingestion. RESULTS: We found serum levels of both eosinophil-derived proteins increased only in challenges including both exercise and suspected food ingestion. Symptoms of anaphylaxis occurred in 3 of these patients. CONCLUSIONS: The increased release of eosinophil basic proteins in PPEIAn patients, caused by physical exercise following ingestion of suspected foods, is not obligatory for the definition of the syndrome.
Adolescent↗
HCV infection in a patient with hyper IgM syndrome.
The association between an acquired form of hyper-IgM syndrome and a chronic hepatitis C virus (HCV) infection in a 71-year-old female patient is described. Both diseases were diagnosed at the age of 58 years. She was started on intramuscular and then intravenous immunoglobulin replacement therapy. HCV RNA was detected in 1992. The patient remained in well-balanced clinical condition until 1994, when total and specific anti-HCV IgM levels increased and the patient developed an IgM kappa monoclonal gammopathy. Adherent cells and B cells were HCV RNA positive, while T cells were HCV RNA negative. Anti-IgM reactivity was specifically directed to the core antigen of the HCV. The patient we describe showed a picture of a late-onset form of hypogammaglobulinemia with a progressive increase in IgM antibodies, possibly due to the concomitant HCV infection. It is possible that the immunodeficiency might also result from the HCV infection, with formation of specific antibodies belonging to the IgM class, and that the worsening of the clinical condition may be directly related to the persistent viral infection.
Aged↗
Hepatitis C virus infection in Italian patients with hypogammaglobulinemia.
We investigated the presence of hepatitis C virus (HCV) infection in 58 patients with humoral immunodeficiencies. Forty-three of these patients had common variable immunodeficiency (CVI), 2 had sporadic hyperimmunoglobulin M (HIM) syndrome, 2 had immunoglobulin G subclass deficiency, 4 had ataxia-telangiectasia (AT), and 7 had X-linked agammaglobulinemia (XLA). Patients with late-onset hypogammaglobulinemia (those with CVI, HIM, or immunoglobulin G subclass deficiency) had a 38.2% prevalence of HCV infection. In patients with XLA or AT, HCV infection was not detectable. Most of the HCV-infected patients had persistent viremia, with histologic findings of chronic hepatitis. Although patients positive for HCV ribonucleic acid (RNA) had received several lots of immunoglobulin, we were unable to detect any correlation between the time that alanine aminotransferase levels increased and the time that intravenous immunoglobulin therapy was given, except in one patient with CVI. Moreover, we found no differences in the number of blood transfusions, surgical procedures, or administrations of intravenous or intramuscular immunoglobulin between HCV RNA-positive and HCV RNA-negative groups. We concluded that: (1) the incidence of HCV infection in patients with hypogammaglobulinemia is much higher than that reported in the Italian general population; (2) although patients with hypogammaglobulinemia have persistent viremia, they do not show an aggressive course of HCV disease, nor does hepatocarcinoma develop; and (3) intravenous immunoglobulins are only one of several possible causes of HCV transmission in patients with humoral immunodeficiencies.
Adult↗
Semen analysis in HIV seropositive men and in subjects at high risk for HIV infection.
The main purpose of this research was (i) to perform a comparative study of sperm parameters in human immunodeficiency virus (HIV) seropositive and high risk subjects in order to identify any possible alterations in the semen which specifically result from HIV infection and (ii) to study the p24 antigen as an early diagnostic marker of infection in high risk subjects. HIV seropositive subjects showed no significant variations regarding sperm densities, motility and viscosity compared to high risk subjects and controls. On the other hand, these HIV seropositive subjects showed (a) a significantly higher percentage of cytoplasmic droplet forms and immature germ cells, perhaps caused by an early failure of epididymal function and/or by a condition of stress affecting spermatogenesis after HIV infection and (b) a significantly higher level of spermiophage cells, suggesting that HIV activates mechanisms that increase spermiophagy. In addition, HIV seropositive men showed a significant positive correlation between blood CD4+ and sperm motility as well as a significant inverse correlation between CD4+ and sperm abnormalities. This is perhaps due to a decrease in testosteronaemia leading to defective epididymal sperm maturation. To date, p24 has not been found in the serum or seminal plasma of high risk subjects. The longitudinal study in progress should provide further information on this point.
Adult↗
Immunological aspects of patients with HIV-1 disease following immunization with recombinant gp160 (VaxSyn).
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AIDS Vaccines↗
Acquired immunodeficiency without HIV infection: epidemiology and clinical outcome in Italy. The Italian Study Group on non-HIV AIDS.
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CD4 Lymphocyte Count↗
Apoptosis-related mortality in vitro of mononuclear cells from patients with HIV infection correlates with disease severity and progression.
Peripheral blood mononuclear cells (PBMC) from 103 HIV-infected patients were tested for their mortality rate (MR) when incubated in vitro for 3 days in a culture medium. MR was related to apoptosis as shown by DNA analysis and morphological evaluation of ethidium bromide-stained PBMC by flow cytometry. MR was significantly higher in patients in CDC stage IV as compared to patients in stage II or III (p = 0.017). MR was also higher in patients with low CD4 cells/mm3 (p = 0.014 for patients with < 400 cells; p = 0.001 for patients with < 200 CD4 cells/mm3) and with low percentage of CD4 cells (p = 0.001 for patients with < 10% of CD4 cells). A significant negative correlation was observed between MR and both absolute numbers or percentages of CD4 cells (p < 0.001). The addition of interleukin-2 (IL-2) and fibro-blast-conditioned medium (FCM) to the cultures significantly reduced MR. However, the ability of both IL-2 and FCM to preserve viability was significantly associated with p24 negativity. Clinical and immunological follow-up was available for 60 patients for a mean period of 26 months. MR at the beginning of the study was significantly higher in the group of patients who clinically progressed (according to the CDC classification) or died during the follow-up (p < 0.0001). Our data suggest that MR correlates with both disease severity and progression and that MR is directly related to the depletion of CD4 cells in cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗