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Biomedical subjects

F Aiuti

Publications and source records attributed to F Aiuti.

At least 91 records · Page 5Linked to original sources
PubMed1993

Fibroblast-derived factors preserve viability in vitro of mononuclear cells isolated from subjects with HIV-1 infection.

OBJECTIVE: Peripheral blood mononuclear cells (PBMC) from HIV-infected subjects have an increased mortality rate (MR) when incubated in vitro for 3 days in a culture medium. We have previously shown that fibroblast-conditioned medium (FCM) can preserve viability, without significant activation, of human lymphocytes in vitro. We therefore tested the ability of two FCM and other factors to reduce spontaneous MR in HIV-positive PBMC. METHODS: PBMC were cultured for 3 days in control medium and medium supplemented with FCM or recombinant cytokines [interleukin (IL)-2, IL-6, IL-7, granulocyte macrophage colony-stimulating factor]. Cells viable at day 3 were counted in a cytofluorimeter after staining with ethidium bromide. DNA was extracted from the cultures and evaluated for the presence of low molecular weight fragmentation. RESULTS: The MR of PBMC from 51 HIV-positive subjects and from 21 healthy controls were 30.1 and 9.5%, respectively (P < 0.0001). The MR was higher in 40 patients with a CD4+ lymphocyte count < 400 x 10(6)/l than in subjects with a count > 400 x 10(6)/l (32.84 versus 20.96%; P = 0.047). IL-2 and FCM significantly reduced MR in HIV-positive subjects (MR: 17.8 and 20.4%; P: < 0.001 and 0.005, respectively). This effect was more evident in subjects with a CD4+ lymphocyte count < 400 x 10(6)/l and in subjects with negative p24 antigenaemia. Cellular proliferation accounts for increased survival in IL-2-supplemented cultures but not in those with FCM. DNA was extracted from fresh PBMC and cells cultured for 3 days for 22 HIV-positive cases. DNA degradation was documented and bands related to an apoptotic mechanism of death observed, especially in subjects with more advanced disease. CONCLUSIONS: Our data suggest that FCM inhibits accelerated cell death in vitro of PBMC isolated from HIV-positive patients.

Adult↗
PubMed1993

Increased IL-6 gene expression and production in patients with common variable immunodeficiency.

We have studied IL-6 gene expression and production by in vitro stimulated peripheral blood mononuclear cells (PBMC) isolated from common variable immunodeficiency (CVI) patients. A strong hybridization signal for the IL-6 probe was observed in mRNA extracted from phytohaemagglutinin (PHA)- and PHA/phorbol myristate acetate (PMA)-stimulated PBMC from most of 12 CVI patients analysed. IL-6 production by PHA-stimulated PBMC from 28 CVI patients was evaluated in ELISA and found to be significantly (P < 0.0001) higher than in normal controls. IL-6 production, however, did not correlate with the lymphocyte populations examined, nor with the absolute number of monocytes. We have also showed that IL-6 was able to increase IgM secretion by several Epstein-Barr virus (EBV)-transformed cell lines derived from both normal donors and CVI patients, but it failed to modify substantially the amounts of IgM and IgG produced in vitro by PBMC derived from CVI patients and activated with pokeweed mitogen (PWM) or anti-IgM. Our data indicate that IL-6 gene expression and production is increased in CVI, but CVI cells do not respond to IL-6 with increased production of immunoglobulin.

Adolescent↗
PubMed1993

Anticandidal activity and interleukin-1 beta and interleukin-6 production by polymorphonuclear leukocytes are preserved in subjects with AIDS.

Polymorphonuclear granulocytes (PMN; or neutrophils) from uninfected or human immunodeficiency virus-infected subjects were tested for their ability to inhibit growth of Candida albicans and produce interleukin-1 beta (IL-1 beta) and IL-6 in vitro. It was seen that PMN from AIDS (Centers for Disease Control stage IV) patients expressed equal if not greater anticandidal activity compared with the activity expressed by neutrophils from all other subjects examined. On exposure to granulocyte macrophage-colony-stimulating factor or to a mannoprotein constituent (MP-F2) from C. albicans itself, PMN from AIDS patients showed enhanced antifungal activity and production of remarkable quantities of IL-1 beta and IL-6. These findings suggest that the functional abilities of PMN to inhibit Candida growth and secrete relevant proinflammatory and immunomodulatory cytokines are intrinsically preserved in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Abnormalities of lymphocyte subpopulations in CVI do not correlate with increased production of IL-6.

We have determined the percentages and absolute numbers of lymphocyte subpopulations in 49 patients with common variable immunodeficiency (CVI). In vitro production of IL-6 by PHA-stimulated PBMC of 28 patients was also evaluated. Our data indicate profound alterations in the lymphocyte subpopulations evaluated, including increased CD8 cells (these cells outnumbered CD4 cells in 26 cases), severe defect of CD4 cells (< 400/mm3) in 10 cases and reduction of CD19 cells (< 50/mm3) in 11/41 cases. Increased production in vitro of IL-6 by PBMC of CVI patients does not correlate with the absolute numbers of lymphocytes, lymphocyte subpopulations, or monocytes. In addition, IL-6 was unable to significantly modify the amount of PWM-driven IgM production by CVI cells.

Adolescent↗
PubMed1992

Modulation of human natural killer activity by vasoactive intestinal peptide (VIP) family. VIP, glucagon and GHRF specifically inhibit NK activity.

Vasoactive intestinal polypeptide (VIP) is a neuropeptide, which also modulates some immune functions. Natural killer (NK) cell activity was already found to be diminished by VIP. In the present paper we report that VIP is able to decrease NK cell activity of human large granular lymphocytes (LGL), showing maximal inhibition at doses ranging from 10(-8) to 10(-6) M. Some neuropeptides, belonging to the VIP family (secretin, glucagon, peptide histidine isoleucine, PHI and human growth hormone releasing factor, GHRF), were also tested. Among these peptides, secretin and PHI were shown to be uneffective on NK cell activity whereas glucagon and GHRF were inhibitory. The D50 of GHRF was similar to that of VIP (10(-9) M), the D50 of glucagon was 10(-8) M. A recently synthesized VIP-antagonist (4Cl-D-Phe6-Leu17) was then used to assess its ability to reverse the VIP-mediated inhibition of NK activity. The antagonist was able to completely reverse the inhibitory effect of VIP on NK activity. The VIP-antagonist was also able to reverse the inhibitory effect of glucagon and GHRF, even though to a lesser extent than for VIP. Our data provide a new physiological observation regarding the functional activity of LGL, supporting the presence of a receptor for VIP on human LGL with NK activity.

Cell Line↗
PubMed1992

Absence of antibodies to human herpesvirus-6 in patients with slowly-progressive human immunodeficiency virus type 1 infection.

To evaluate a possible role for Human Herpesvirus-type 6 (HHV-6) coinfection as a co-factor in the progression of HIV-1 disease, we investigated the prevalence of seropositivity for HHV-6 in a cohort of HIV-1 infected patients. These patients were retrospectively divided into two groups according to the decline of CD4+ T cells during the follow up: 11 were classified as rapid decliners (less than 400 CD4+/cmm within 1 year), and 38 as slow decliners (greater than 400 CD4+/cmm after at least 4 years' follow up). HHV-6 antibodies were detected by a commercial immunofluorescence assay and by a Western blotting assay developed in our laboratory. Our results show that Western blot appears to provide results satisfactorily free of false positivities. We found that the frequency of HHV-6 seropositivity was significantly lower in the group of slow decliners, compared both to rapid decliners and to the general population. These data suggest a role for HHV-6 co-infection in the progression of HIV-1 disease.

Adolescent↗
PubMed1992

Selective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia-telangiectasia.

Several immunological abnormalities have been observed in ataxia-telangiectasia (AT), the most consistent being defects of immunoglobulin isotypes, decreased T-cell numbers, and reduced proliferative responses to mitogens. We examined the distribution of T lymphocytes expressing distinctive surface Ag characteristic of "naive" (CD45RA+) and "memory" (CD29+, CD45RO+) T cells, in both CD4+ and CD8+ (bright and dim) lymphocytes from 13 AT patients, compared with healthy age-matched controls. We found that, irrespective of age, patients with AT had a severe deficiency of CD4+/CD45RA+ lymphocytes. This decrease accounted for the reduction of total CD4+ cells, since the absolute numbers of memory CD4+ cells were not significantly different in AT and in controls. Functional tests revealed poor proliferative responses to phytohemagglutinin and normal responses to soluble Ag (tetanus toxoid) in AT patients. These data fit with the distribution of naive and memory cells, which are known to respond predominantly to mitogens or to recall Ag, respectively. CD45RA molecules were normally expressed on CD8+ lymphocytes. This rules out a generalized defect of regulation or differential splicing as the cause of defective expression of CD45RA on CD4+ cells. The selective deficiency of CD4+CD45RA+ may provide a cellular basis for some functional T-cell abnormalities of AT patients. Furthermore, it might practically serve for an early, or even prenatal, diagnosis of this disease.

Adolescent↗
PubMed1992

Parvovirus infection in children with AIDS: high prevalence of B19-specific immunoglobulin M and G antibodies.

OBJECTIVE: Investigation of the prevalence and pathogenic role of parvovirus B19 infection in Italian and Rumanian children with AIDS, compared with age-matched HIV-negative children (controls) with various recurrent infections of unknown aetiology. DESIGN: Detection of B19-specific immunoglobulin (Ig) M and IgG antibodies as the most indicative markers of past or current B19 infection. METHODS: B19 antibodies were detected by two enzyme immunoassays using synthetic peptide or recombinant protein, which corresponded to different B19 epitopes, as coating antigens. RESULTS: B19 IgM and IgG were seen in 10 out of 20 (50%) Italian and in 20 out of 51 (39.2%) Rumanian children with AIDS, in contrast to none out of 17 Italian and one out of 22 Rumanian controls (P less than 0.001). In addition, two Italian controls (11.8%), two Rumanian children with AIDS (3.9%), and two Rumanian controls (9.1%) had B19 IgM alone. Specific IgG alone was detected in eight (40%) Italian and 14 (27.5%) Rumanian children with AIDS, and in seven (41.2%) Italian and four (10.2%) Rumanian controls. CONCLUSIONS: While it is possible to attribute some B19 infections in Rumanian children to blood transfusion, the source was unknown for Italian children. However, in three of the Italian children who had B19 IgM and IgG persistently for 15-22 months, and in a 2-month-old Italian infant with B19 IgM and IgG, HIV might have activated a congenital or perinatally-acquired B19 infection.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Spectrotype of anti-gp120 antibodies remains stable during the course of HIV disease.

Human immunodeficiency virus (HIV) infection is characterized by a progressive decline in immune functions. The behavior of B-cell clones specifically engaged in the anti-HIV response could play a relevant role in the pathogenesis of such impairment. The spectrotype observed on isoelectric focusing and reverse blotting after antigen challenge is the serum image of antigen-specific B-cell activity and may provide some insight into Ag-dependent B-cell clone recruitment. In this study, we examined the spectrotype of anti-gp120 antibodies in a group of sera from 56 HIV-infected patients, belonging to groups II, III, and IV of the Centers for Disease Control classification, as well as in a group of 31 sera from 12 patients in a 21-month follow-up evaluation (range 7-36 months). All tested sera were positive for gp120 antibodies on Western blot. In the first group of 56 HIV-infected subjects, only 19 displayed well-focused banding patterns. Among these, the spectrotype was found to be consistently oligoclonal, thus confirming clonal restriction of anti-gp120 antibodies previously described by other investigators. No correlation could be established between a particular spectrotype and phase of the disease. The follow-up evaluation in the second group of 31 sera revealed the tendency in each patient to maintain the same spectrotype throughout the course of the disease. These findings confirm clonal restriction of anti-gp120 antibodies in HIV infection and suggest that the number of B-cell clones recruited in the anti-gp120 response remains stable over the course of the disease, at least in the time range explored by us.

Adult↗
PubMed1992

[The clinical and immunological efficacy of a combination of immunoglobulins and an oral polyvalent antibacterial vaccine in recurrent respiratory infections].

Ninety patients with a history of recurrent upper and lower respiratory infections were randomized into three groups of 30 patients each. Group 1 was treated with i.m. immunoglobulins and oral polyvalent bacterial vaccine, group 2 with vaccine only, while group 3 was not submitted to prophylactic treatment. During and after prophylaxis, all three groups were evaluated for frequency of recurrent respiratory infections and the most relevant immunological parameters. In groups 1 and 2, a significant reduction of minor and major upper and lower respiratory infections was observed compared to the control group. Patients treated with Ig+vaccine or vaccine alone showed an increase of IgG2 subclasses and CD4 lymphocytes and positive changes of delayed skin tests. These findings confirm the results of previous preliminary studies which had shown the polyvalent bacterial vaccine to be useful for the reduction of recurrent infections of the respiratory tract, especially during the winter. Further studies will have to be carried out in order to identify the precise mechanism by which antigen stimulation with the oral vaccine improves the immunological response of the respiratory tract.

Administration, Oral↗