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Biomedical subjects

M Fiorilli

Publications and source records attributed to M Fiorilli.

At least 73 records · Page 4Linked to original sources

Cell-mediated immunity in human cytomegalovirus infection.

The direct leukocyte migration inhibition test, in response to cytomegalovirus stimulation, was used to study cell-mediated immunity in a group of children with cytomegalovirus infection. The test was impaired in children with chronic disease associated with cytomegaloviruria. In those cases with no viruria at the moment of the test, leukocyte migration inhibition was normal. Our data suggest that the acquired chronic cytomegalovirus infection may be sustained by a state of specific cellular desensitization, as already demonstrated for congenital infection.

Cell Migration Inhibition↗

Monoclonal antibody analysis of T cell subsets in 40 patients with immunodeficiencies.

A panel of previously characterized monoclonal antibodies: OKT3, OKT4, OKT8, OKT10, OKT11, OKIa1, OKM2; 3A1, 4F2, UCTH1 and 5/9 were used to evaluate peripheral blood mononuclear cells in patients with severe primary immunodeficiencies: three patients with severe combined immunodeficiency, five with X-linked agammaglobulinemia, 20 with common variable hypogammaglobulinemia, 11 with IgA defect, and one with an unclassified form of T cell defect and hypogammaglobulinemia. Surface markers for T and B cells and in some cases functional assays, were also performed. Our results indicate a heterogeneous pattern in patients with severe combined immunodeficiency: one had peripheral blood mononuclear cells negative with all the monoclonal antibodies used; one had an increase in OKM2+ cells, whereas OKT3+ cells were absent; one had defect and imbalance of immunoregulatory T cell subpopulations. Major imbalances of T cell subsets were not detected in patients with X-linked agamma and IgA defect, whereas in some patients with common variable hypogammaglobulinemia an inversion of the physiological ratio between OKT4+ and OKT8+ cells was consistently detected. In an unclassified case of primary immunodeficiency, almost all peripheral blood mononuclear cells formed rosettes with sheep erythrocytes, but lacked antigens detected by monoclonal antibodies. Based on these observations, possible sites of defects in the T cell differentiation are discussed. We believe that monoclonal antibodies are useful for diagnosis, classification, and monitoring of therapy of primary immunodeficiencies.

Adolescent↗

Enhancement by TP-1, a thymic extract, of pokeweed mitogen-induced differentiation of B cells from normal subjects but not of those from patients with systemic lupus erythematosus.

We studied the ability of TP-1, a calf thymic extract, to influence in vitro pokeweed mitogen (PWM)-induced plasma cell generation and blastogenesis of peripheral blood lymphocytes from normal donors and from patients with systemic lupus erythematosus (SLE). In normal subjects, TP-1 significantly increased plasma cell generation, but did not affect the mitogenic response to PWM. On the contrary, differentiation of B cells from SLE patients was not enhanced by this extract. The action on the differentiation of normal B cells could either be due to a direct effect on B cells or be mediated by activation of helper T cells.

Animals↗

T-dependent immunity in aged humans. I. Evaluation of T-cell subpopulations before and after short term administration of a thymic extract.

T lymphocytes, T lymphocyte subpopulations and delayed hypersensitivity reactions to recall antigens were studied in 20 aged subjects clinically unaffected by disorders of the immune system. T-cells evaluated by the sheep rosette test and absolute T-cell number were within normal range. T-cell subsets were studied by the high affinity rosetting test and by the sheep rosette test after pre-incubation with theophylline; such methods have been shown by others to discriminate between T-cells with helper or suppressor activity. We did not observe an imbalance of such subpopulations. Skin reactivity to recall antigens (Candida and SK-SD) was depressed in several cases. Since a decline in serum levels of thymic hormones has been reported in the ageing and it is suggested that this could account for the T-dependent immunity defect, we treated these patients with a bovine thymic extract (thymostimulin, TP-1) 1 mg/kg/day for three consecutive days. Immunological tests were performed again after this therapy but no modifications were observed. We may conclude that the aged subjects studied in this paper present normal relative and absolute number of T-cells and T subpopulations, whereas the function of T-cells, as assessed by skin reactivity to recall antigens is often depressed. Short term therapy with TP-1 at the above mentioned dosage was ineffective in modifying the parameters analysed.

Aged↗

Imbalances of T cell subpopulations in primary immunodeficiencies and systemic lupus erythematosus.

In the present report we describe a recently proposed technique for the enumeration of T lymphocyte subpopulations. The study was performed on peripheral blood lymphocytes (PBL) of 21 patients with primary immunodeficiencies and 10 with systemic lupus erythematosus (SLE). With this methodology, sheep rosettes are evaluated before and after preincubation with theophylline. Previous reports have shown that cells rosetting after the preincubation (T-res) contain most of the percentages of the helper activity, whereas sensitive cells (T-sens) exert suppression. T-res and T-sens cells were compared to several clinical and immunological parameters, including the detection of lymphocytes with Fc IgM and IgG receptors. We demonstrated a significant positive correlation between T-res and and EAox IgM cells and between T-sens and EAox IgG cells. In addition, patients with Ig defects demonstrated heterogeneity regarding alterations in the proportions of T-res and T-sens cells. On the contrary, in 8 patients with SLE, there was a markedly reduced proportion of T-sens cells. Variations in the balance of subpopulations were observed after treatment with thymic hormones and levamisole. We may conclude that theophylline rosettes represent an easy technique that can be profitably used in the evaluation of T cell subpopulations in immunological diseases.

Adult↗

Formalin-treated bacteria as selective B cell mitogens: results in primary and acquired immunodeficiencies.

The mitogenic activity of the formalin-treated bacterial strains Branhamella catarrhalis, Haemophilus influenzae and the Cowan I strain of Staphylococcus aureus was assessed in peripheral blood lymphocytes (PBL) from patients with primary immunodeficiencies, acute lymphocytic leukaemia (ALL), chronic lymphocytic leukemia (CLL) and in umbilical cord blood lymphocytes. The bacteria selectively stimulated B cells, as demonstrated by the finding of a normal de novo DNA synthesis in children with a T cell defect and of an absent response in X-linked agammaglobulinaemia and severe combined immunodeficiency. A decreased mitogenic activity was exerted on PBL from four out of seven adults with common variable hypogammaglobulinemia (CVH). In B-CLL the mitogenic activity was normal while in T-ALL it was decreased. Umbilical cord blood lymphocytes responded better than PBL from adults. The selective stimulative ability of the bacteria for B lymphocytes is expressed when PBL are cultured together with the formalin-treated bacteria for 48 to 72 hr.

Adolescent↗

Improvement of natural killer activity and of T cells after thymopoietin pentapeptide therapy in a patient with severe combined immunodeficiency.

The case of an 18-month-old child, affected by malnutrition, severe interstitial pneumonia and immunological abnormalities is reported. Since the age of 10 months, the infant suffered from severe recurrent infections and failure to thrive. Immunological studies revealed a striking decrease of T lymphocytes and of natural killer (NK) function. Serum immunoglobulins, salivary IgA, natural isohaemagglutinins, Fc-IgG receptor-bearing cells and suppressor T lymphocytes were absent, together with an impaired de novo DNA synthesis after PHA, Con A, PWM and Cowan I strain from Staphylococcus aureus stimulation. In vitro incubation of the patient's lymphocytes with TP-5, a thymopoietin-derived synthetic pentapeptide, resulted in improvement of sheep rosettes, Fc-IgG receptor-positive lymphocytes and NK activity. The child was therefore treated with TP-5 for 8 months and his clinical condition improved as well as the number of T cells, Fc-IgG-positive lymphocytes and NK function. However, humoral immunity remained persistently depressed. We suggest that this child could be classified as affected by 'late-onset severe combined immunodeficiency'. In vitro assays with thymic hormones or synthetic drugs that mimic the action of thymic hormones should be performed and this therapy could be applied in the treatment of some of these heterogeneous syndromes, especially when an immunological reconstitution with bone marrow or fetal graft cannot be attempted.

Antigens↗

Response to B and T cell mitogens and surface markers in human fetal lymphoid tissues.

We studied the responses to phytohemagglutinin (PHA) and Staphylococcus aureus protein A (SpA), a B cell mitogen, and surface markers in the thymus, liver and spleen of 5 human fetuses ageing from 12 to 26 gestational wk and in cord blood lymhocytes of 9 newborns. Sheep rosette forming cells appeared in all 3 organs at 17 wk; mIgM+ cells were detected in liver and spleen at 24 and 17 wk respectively. SpA and PHA stimulated the cells of all the 5 liver and all the 3 spleen samples examined. Thymus cells responded to PHA as early as the 17th wk and showed a progressive increase in stimulation indexes. An unexpected observation was the response of the thymus cells of a 15-wk fetus to SpA; this finding is discussed in the text. Cord blood lymphocytes gave results comparable to those found in normal adults.

B-Lymphocytes↗

Immunologic and clinical investigation on a bovine thymic extract. Therapeutic applications in primary immunoedificiencies.

Thirteen patients with primary immunodeficiencies (eight with T-cell deficiency, one with Wiskott-Aldrich (W-A) syndrome, two with common variable agammaglobulinemia (CVA), and two with severe combined immunodeficiency (SCID) were treated with a calf thymus extract, called thymostimulin (TS). It has been shown that this extract causes in vitro differentiation of T-cell precursors in patients with T-cell defect. Five of eight patients with pure T-cell defect showed immunologic recovery and clinical remission lasting for several months after interruption of the therapy; one had only transient reconstitution, one had slight increase in T-cells (clinical conditions not yet estimated), and two patients soon died from severe infections after showing a slight increase of T-cells. Immune recovery was assess by an increase of the absolute number of E-rosettes forming cells, of human T-lymphocyte antigen positive cells and of PHA responsiveness in the peripheral blood, and by a positive delayed hypersensitivity reaction to antigens. In five patients, there was also B-cell increase after TS treatment. Clinical remission consisted of disappearance of infections, weight gain, and in improvement in general conditions. No effect was observed in one patient with W-A syndrome, in two with CVA, and in two with SCID. Several hypotheses on the mechanisms involved in immune reconstitution are discussed. It seems likely that TS acts on prethymic cells or on the epithelial cells of hypoplastic thymuses. TS was not effective, either in vitro or in vivo, in patients with SCID probably because of a defect in stem cells.

Agammaglobulinemia↗

Specific cellular unreactivity during cytomegalovirus infection in man.

The specific cellular immune response against Cytomegalovirus (CMV) was studied by the Leucocyte Inhibitory Factor (LIF) production test in three groups of subjects: 7 healthy individuals with no CMV antibodies, 4 with antibodies to CMV but without evidence of active infection, and 2 children with clinical CMV infection. Our results show that LIF production in presence of CMV is high in normal seropositive subjects, while it is strongly deficient in patients with active infection, despite a good humoral response to the virus. In one child with congenital infection, a low number of E rosette forming cells was also revealed. We suggest that CMV infection can induce, at least during infancy, a state of specific cellular unresponsiveness to the virus. When the infection is congenital, a generalized depression of the cellular immune system may develop.

Antibodies, Viral↗

Effect of thymic factor on human lymphoid cells of umbilical cord blood and of children with T cell deficiency.

We report on the in vitro effect of a thymic factor (TF) extracted from pig thymuses, on human lymphoid cells from umbilical cord blood and from peripheral blood of 8 T cell-deficient patients. E rosette formation was not affected by TF when tested on cells from peripheral blood of normal adults. With cells from umbilical cord blood of 13 healthy, full-therm newborn babies, the difference between the percent (mean) of ERFCs before (16.31 +/- 11.13) and after (28.85 +/- 17.10) incubation with TF was statistically significant (p less than 0.05). In most samples, TF transformed about 10-20% of the cells. In the T cell-deficient group the increase in ERFCs of the peripheral blood lymphocytes, though consistent, was variable in degree from case to case. Our data indicate that precursor cells in some individuals with T cell deficiency are very sensitive to TF. Patients with highly responsive precursors appear to be the best candidates for a therapeutic approach with TF when thymus transplant is not possible.

Child↗

Lymphoid cells in infectious mononucleosis classified according to T and B cell markers.

It has been demonstrated that peripheral blood lymphocytes, particularly the "atypical" ones, are predominantly of the T type in infectious mononucleosis (IM). This is based on membrane marker studies (E rosettes, receptor for complement, receptor for Fc fragment of immunoglobulins (Ig), and membrane Ig) and by anti-T lymphocyte serum. On the other hand, lymphoblastoid cell lines derived from IM patients show the characteristics of B lymphocytes. This permits the suppostion that EBV infects B lymphocytes and stimulates them to proliferate. The cell proliferation is unlimited in vitro and is probably controlled in vivo by T cells. The reduction of cellular immunity in vivo, which contrasts with the high number of T cells in peripheral blood, could be explained by the fact that T cells are engaged in the regulation of B cell proliferation.

Animals↗