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Biomedical subjects

G Candore

Publications and source records attributed to G Candore.

At least 37 records · Page 2Linked to original sources
PubMed1999

Granulocyte and natural killer activity in the elderly.

The deterioration of the immune system in ageing, 'immunosenescence', is thought to contribute to increased morbidity and mortality from infections and possibly autoimmune diseases and cancer. The most profound changes involve effector and immunoregulatory T-cell functions. Immunosenescence appears also to be related to changes in non specific immunity as well. In the present study we have assessed superoxide production, chemotaxis and the expression of the apoptosis-related molecule APO1/Fas (CD95) on neutrophils (PMN) from young and old subjects. Furthermore, we have measured the basal natural killer (NK) activity of young and elderly subjects and we have compared the number of CD16+ cells found in these two groups. We observed a significant decrease age-related both of formation of O2- and chemotaxis whereas no significant correlation between age and the expression of CD95 on granulocyte membrane was demonstrated, suggesting that an increase age-related of CD95-linked apoptosis of PMN should be not an important determinant in the decreased PMN function. We also observed a significant correlation between age and NK activity. The decreased NK cell function was not due to a decreased number of NK cells in effector cell preparations since the number of CD16+ cells was significantly increased in old subjects. In conclusion, our results show that in the elderly there is also a deficit of the aspecific immunity that might play a role in the pathogenic mechanisms of the immunosenescence.

Adult↗
PubMed1999

Interleukin-5 production by mononuclear cells from aged individuals: implication for autoimmunity.

It is well known that in the elderly a deterioration of immune functions may occur. Particularly, stimulation of T cells from aged individuals leads to different kind and/or size of responses if compared with the responses obtained from T cells from young individuals. At the same time, an increase in prevalence of autoantibodies occurs in elderly. The altered production of certain cytokines might explain this paradox of decreased responsiveness to foreign antigens in the face of an increased response to self-antigens. We and others have suggested that this kind of immune response might depend on an age-associated impairment of Th-1 type function that selectively affects production of cytokines involved in the control of cellular responses. In contrast, Th-2 type function is seemingly not affected in elderly, as suggested by normal in vitro production of cytokines involved in humoral responses. To strengthen this hypothesis, in this study we have analysed the influence of age on the ability of mitogen-stimulated cultures of peripheral blood mononuclear cells from human beings to produce another Th-2 type cytokine, i.e. interleukin-5 (IL-5). IL-5 content of both 24- and 48-h stimulated cultures from old individuals was greater than that of young ones, although this difference attained significance only at 48 h. We suggest that the decreased production of Th-1 type cytokines in the presence of a normal or even increased production of Th-2 type cytokines might account for the pattern of immune response which may be observed in elderly, i.e. a normal or increased humoral response, including an autoimmune one, in the face of a low cell mediated immune response.

Adult↗
PubMed1999

Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes.

Aging is associated with alterations of the immune system, thought to be related to an increased susceptibility to infectious diseases, and possibly to cancer and autoimmunity in the elderly. In the present paper we report data obtained on freshly collected blood from 148 healthy subjects of different ages (from cord blood to 102 years old). The subjects were divided into seven age classes (cord blood, 3-11 years, 15-39 years, 41-60 years, 61-74 years, 75-84 years, 85-102 years) and their lymphocyte subsets and the expression of the apoptosis-related molecule CD95 were evaluated. In respect of lymphocyte subsets, the major differences were found in the cord-blood samples compared with the oldest old groups. In the cord-blood group, the absolute number of all the lymphocyte subsets was enhanced, but in the oldest group, an increase of CD16+ lymphocytes was observed, whereas CD19+ lymphocytes, which progressively decrease with age, continue to decrease further in the very old. The data show that the expression of CD95 increases until age 74 years, whereas in the oldest old it tends to decrease again. The trend of CD95 expression seems to be related to the change of expression of CD95 on CD4+ lymphocytes, because the CD8+/CD95+ population rose steadily throughout the entire age range. The evaluation of CD95+/CD45R0+ lymphocytes shows similar results to those observed analyzing CD95 on total lymphocytes. Furthermore, a constant increase of CD95+/CD28+ and a related decline of CD28+ lymphocytes was observed in all age groups. These data suggest that the expression of CD95 on the different subsets of lymphocytes can be considered a good marker for studies of immunosenescence, because it may be predictive of successful aging, and can partially explain the change in lymphocytes subsets in elderly.

Adolescent↗
PubMed1999

Comparison of the effects of fluticasone propionate, aqueous nasal spray and levocabastine on inflammatory cells in nasal lavage and clinical activity during the pollen season in seasonal rhinitics.

BACKGROUND: Treatment options for allergic rhinitis include antihistamines, decongestants, anticholinergics, cromolyn sodium and corticosteroids. As the nose is a small organ, comprising less than 1% of total body mass and surface area, it seems logical to confine treatment of rhinitis to the diseased organ. OBJECTIVE: To evaluate the effects of therapy with intranasal fluticasone propionate (FP), both on subjective symptoms and pathophysiological mechanisms, in rhinitis patients during pollen season when the patients were symptomatic. METHODS: We used a double-blind, placebo (PLA)-controlled, randomized, double dummy, parallel group study of the effect of 6 weeks treatment. The double-blind comparison was made between the following three treatments: FP aqueous nasal spray, 200 microg taken once daily, levocabastine (LEV) nasal spray, 200 microg taken twice daily and PLA nasal spray. Clinical evaluation and the levels of cells and mediators in nasal washing were performed before and after treatments. Twenty-four patients (11 men and 13 women, aged 17-50 years, mean age 30.1 +/- 8.5) with strictly seasonal allergic rhinitis to Parietaria entered the study. Clinical evaluation and the levels of inflammatory cells (eosinophils and activated eosinophils, i.e. EG2+) and their mediators (tryptase, eosinophil cationic protein, eosinophil protein X and neutrophil myeloperoxidase) in nasal-lavage were performed before and after treatments. RESULTS: Treatment with FP significantly increased, with respect to placebo, the percentage of days without sneezing (P < 0. 001), nasal blockage (P < 0.001), rhinorrhea (P < 0.001), nasal itching (P < 0.001). Furthermore, treatment with FP showed additional benefits with respect to LEV. The percentage of days without nasal blockage was significantly higher in the FP group that in the placebo group (P = 0.018). The same applied to rhinorrhea (P = 0.009). The percentages of days without sneezing and itching were instead not significantly different between the two groups. As expected, no significant differences were observed in baseline medians of the rhinitis symptom scores as well as in mean values of all mediators and eosinophils in nasal lavages of the various groups under study. After treatment the mean of subjective symptoms as well as all values in nasal lavage level fell significantly only in the FP group, whereas no significant changes were observed either in LEV or PLA groups. Accordingly, significant differences were observed at the end of the treatments between the values of fluticasone group vs LEV and PLA group values. Significant correlations between these values and symptom scores were found, according with literature data suggesting a pathogenetic role for these mediators and eosinophils in rhinitis. CONCLUSION: FP (200 microg once daily) affords a significant degree of improvement in rhinitis control during pollen season, as measured by subjective and objective parameters, compared with LEV (200 microg twice daily) and PLA. The therapeutic benefits of intranasal FP are reflected in, and may be caused by, the decrease in nasal inflammatory cells.

Administration, Topical↗
PubMed1998

Interleukin-12 release by mitogen-stimulated mononuclear cells in the elderly.

Defects involving cellular expression of activation molecules, cell mediated immune response and natural killer (NK) activity are commonly observed in the elderly. Herein, data are reported on the evaluation of IL-12 production by old subjects. IL-12 is, actually, considered the key molecule for the induction of a T helper 1 (Th1) -type and NK response. IL-12 production from old subjects peripheral blood mononuclear cells (PBMNC) was evaluated using T-independent (bacterial lipopolysaccharide, LPS) or -dependent (phytoemagglutinin, PHA; immobilized anti-CD3 monoclonal antibodies, anti-CD3) mitogens. The IL-12 production after LPS stimulation was not reduced in cultures from old subjects when compared to that from young ones. On the contrary, IL-12 production by PHA or anti-CD3 stimulated PBMNC from old subjects was decreased. Furthermore, we have demonstrated a reduced CD40 and CD40 ligand (CD40L) expression on PBMNC from old subjects. This finding fits very well with the reduced cytokine production observed in the T-dependent stimulation systems, being the CD40-CD40L interaction mandatory for an efficient IL-12 production. All together, these results seem to suggest that defects in cell expression of activation molecules can affect the IL-12 secretion and in consequence other Th1-type cytokines.

Adult↗
PubMed1998

Apoptosis and ageing.

Stimulation of T cells from aged individuals leads to different kinds and/or size of responses if compared with the responses of T cells obtained from young individuals. In fact elderly is associated with a progressive decline of immune response besides an increasing incidence of autoimmune phenomena. These differences might be the result of modified cellular mechanisms controlling the immune system in the course of ageing. The apoptotic deletion of activated T cells has been proposed as the key mechanism to maintain T cell homeostasis, and in this respect CD95 (Fas antigen) seems to play a major role in this course of events. In this study we show that just collected lymphocytes from old subjects displayed an increased expression of the apoptosis molecule CD95. The expression of CD95 and the spontaneous apoptosis showed the same trend. In fact the percentage of apoptotic cells in blood collected from old subjects was enhanced too. The lymphocyte subpopulation analysis by flow cytometry did not show significant changes in T subset percentages between old and young subjects. Moreover mononuclear cells obtained from aged individuals underwent apoptosis in culture in response to a single stimulation with mitogen or anti-CD3, more than mononuclear cells from young controls. To gain insight into mechanisms of this increased apoptosis, experiments were performed to evaluate the behaviors of lymphocytes from old and young donors in respect of interleukin-2 (IL-2) rescue from apoptosis. Results show that IL-2 rescued only a little fraction of cells of old donors from apoptosis when activated by anti-CD3 and that this effect was not related to a different expression of CD95. Thus, during the course of ageing the different regulation of T cell homeostasis might be also explained by the modified proneness of lymphocytes to undergo apoptosis. The contemporaneous demonstration of a reduced Ca2+ influx in lymphoid cells of these subjects allows to suppose that multiple defects play a role in the pathogenesis of immunosenescence.

Adult↗
PubMed1998

Biological basis of the HLA-B8,DR3-associated progression of acquired immune deficiency syndrome.

The factors influencing the evolution of human immunodeficiency virus (HIV) infection are not fully known, but the host genotype undoubtedly plays a role in determining the outcome of the disease by affecting the immune response to HIV. The role of the host human leukocyte antigen (HLA) genotype in the regulation of susceptibility to HIV infection and expression has been studied extensively in different major risk groups. Certain HLA alleles and haplotypes, being associated with aberrant immune responses independently from HIV infection, have been reported to facilitate the rapid progression of disorders related to HIV infection. Particularly, the association of rapid acquired immunodeficiency syndrome (AIDS) progression with genes from the HLA-B8,DR3 haplotype has been reported by different research groups. It is well known that this haplotype is associated in all Caucasian populations with a wide variety of diseases with autoimmune features and in healthy subjects with a number of immune system dysfunctions, as a reduced production of T helper (Th)1 type cytokine. HIV infection may act on this genetic background triggering immunopathogenetic mechanisms leading to AIDS with a dominant Th2 profile as a common feature.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Hypothesis: interleukin-5 production impairment can be a key point in the pathogenesis of the MHC-linked selective IgA deficiency.

Selective IgA deficiency (IgA-D) is associated with the expression of some human leukocyte antigens (HLA) haplotypes and Major Hystocompatibility Complex (MHC) gene products have been suggested to be involved in the regulation of IgA synthesis. Recently, we have obtained evidences indicating that MHC influences the production of IgA and interleukin-5 (IL-5) both in humans and in mice. Lymphnode cells from pychril chloride (PC1) immunised BALB/c mice (bearing the H-2d haplotype) fail to produce IL-5 when stimulated in vitro with PC1 and this correlates with low antigen specific IgA production in vivo. In contrast using congenic BALB/k mice (bearing the H-2k haplotype) an high production both of IL-5 and of PC1-specific IgA is observed. Moreover, in vivo or in vitro administration of IL-5 to BALB/c mice was able to increase the production of antigen specific IgA. Similar evidences have been obtained by evaluation of the HLA influence on circulating immunoglobulin levels and interleukin production in normal HLA typed subjects. In fact HLA-B8, DR3 positive subjects show reduced level of serum IgA and their peripheral blood mononuclear cells stimulated with mitogen produce significantly reduced amounts of IL-5, IL-12, IL-2 and Interferon-gamma. We hypothesise that HLA-B8, DR3 associated IgA deficiency, known to be asymptomatic, can be due to a lack of subsequent signals, in particular of IL-5, involved in the late regulation of B cell differentiation. Preliminary evidences demonstrating that low amounts of human recombinant IL-5 are able to reconstitute IgA production by cells from HLA-B8, DR3 IgA-D subjects, seem to confirm this hypothesis.

Animals↗
PubMed1997

Prevalence of organ-specific and non organ-specific autoantibodies in healthy centenarians.

In the present study we have investigated the prevalence of organ-specific and non organ-specific autoantibodies in 26 healthy centenarians (6 men, 20 women; age range 101-106 years), using as controls 54 healthy old (33 men and 21 women, age range 71-93) and 56 young subjects (29 men and 27 women, age range 26-60). We assayed sera of each group for the following organ-specific autoantibodies, anti-gastric mucosa (anti-PCA), anti-thyroglobulin (anti-Tg) and non organ-specific autoantibodies, anti-cardiolipin (anti-APA IgG and IgM), anti-nuclear antigens (anti-ANA), anti-double strand DNA (anti-ds-DNA), anti-extractable nuclear antigens (anti-ENA). Finally, natural anti-alpha-galactosyl (anti-alpha-GAL) antibodies were also analyzed. As expected, in the old subjects there was a significant increase of prevalence of anti-Tg and anti-PCA autoantibodies. By contrast, in centenarians the prevalence of organ specific anti-Tg and anti-PCA antibodies was not significantly different from that observed in controls aged less than 60 years. The prevalence of non organ-specific autoantibodies anti-APA (IgG), anti-APA (IgM), anti-ANA, was significantly increased both in the elderly and centenarians when compared with the prevalence observed in sera from the young. Anti-ENA and anti-dsDNA antibodies were not detected in all groups studied. Finally, the prevalence of natural anti-alpha-GAL antibodies significantly increases with age, including centenarians. In conclusion, we confirm and extend the results previously obtained by other authors. In fact, as already described, the prevalence of organ-specific autoantibodies in the elderly is not seen after the tenth decade of life. Interestingly, the prevalence of non organ-specific autoantibodies is instead increased in these subjects, suggesting that different mechanisms are involved in the pathogenesis of these autoantibodies. Particularly, these autoantibodies could be the expression of a damaged tissue process rather than of an autoimmune one, as suggested by data concerning natural antibodies.

Adult↗
PubMed1997

Allergic rhinitis to grass pollen: measurement of inflammatory mediators of mast cell and eosinophils in native nasal fluid lavage and in serum out of and during pollen season.

BACKGROUND: In allergic rhinitis, mast cells, activated by cross-linking of allergen to mast cell-bound specific IgE, release both vasoactive mediators related to the early nasal symptoms and chemotactic mediators that attract inflammatory cells, such as eosinophils, related to the late-phase response. OBJECTIVE: We have analyzed, during and out of pollen season, in blood and nasal fluid from patients allergic to grass pollen, histamine and tryptase to monitor the early phase markers and eosinophil and eosinophil cationic protein (ECP) to monitor the late phase. METHODS: Twenty patients were enrolled in the study. As a control, we studied 10 nonatopic subjects. Mediators and eosinophils were assessed in blood and nasal fluid. Histamine was tested only in nasal fluid. RESULTS: During pollen season, tryptase but not histamine increased in nasal fluids from patients (2.96 vs 0.22 U/ml, p = 0.001) and correlated with symptom scores (r(s) = 0.63, p = 0.003). Tryptase was not detected in serum. Eosinophils increased in nasal cytology (17.0% vs 2.0%, p = 0.001) and in the blood (265 vs 12.7 x 10(6) L, p = 0.001) from patients, but they did not correlate with symptom scores. ECP increased only in the nasal lavage (1633 vs 1.30 ng/ml, p = 0.001) and correlated with symptom scores (r(s) = 0.53, p = 0.016). CONCLUSIONS: Both ECP and tryptase increase in nasal secretion in natural disease. Therefore the measurement of tryptase and ECP levels in nasal fluid might be a useful clinical test for monitoring disease activity and the effects of therapeutic agents.

Adult↗
PubMed1997

Defective expression of CD95 (FAS/APO-1) molecule suggests apoptosis impairment of T and B cells in HLA-B8, DR3-positive individuals.

Activation-induced apoptosis is one of the primary control mechanisms for the negative selection of an immune response, leading to maintenance of immune homeostasis and selective T cell deletion. The interaction between the surface molecule Fas and its ligand (FasL) has been proposed as a primary mechanism initiating T cell apoptosis. The T cell receptor modulates the expression and function of these molecules. Defects in the Fas/FasL apoptosis pathway have been shown to result in autoimmune disease in humans and in murine models. Because subjects carrying the HLA-B8, DR3 haplotype show a number of immune dysfunctions, including membrano-proliferative glomerulonephritis, systemic lupus erythematosus, Graves' disease, and others, we investigated Fas expression on T and B cells, and sensitivity to Fas-mediated apoptosis of activated T cells, to determine whether abnormalities of the Fas pathway might be associated with the development of autoimmune diseases in this group of individuals. Our findings show that B cells and resting T cells from HLA-B8+, DR3+ subjects express markedly reduced levels of Fas compared with those isolated from HLA-B8-, DR3+ individuals. Reduced levels of Fas were also evident on the surface of T cells from HLA-B8+, DR3+ subjects activated in vitro by stimulation with OKT3 and phytohemoagglutinin. Cycling T cells from these subjects, evaluated for apoptotic nuclei by flow cytometry after incubation with a cytolytic anti-Fas mAb, showed a significantly lower percentage of Fas-mediated apoptosis than did those from HLA-B8-, DR3- individuals. Normal levels of apoptosis were restored after exposure to a synthetic ceramide analog (C2). Further elucidation of the interaction of these molecules in autoimmune diseases may lead to better understanding of the pathogenesis of these disorders.

Antigens, CD19↗
PubMed1997

Non-specific airway hyperresponsiveness in mono-sensitive Sicilian patients with allergic rhinitis. Its relationship to total serum IgE levels and blood eosinophils during and out of the pollen season.

BACKGROUND: Initial attempts to evaluate the association between allergic rhinitis and non-specific bronchial responsiveness has produced conflicting results. In fact, some studies showed a strong correlation and other failed to find an association. However, little is known about the effect of natural specific allergen exposure on the bronchial reactivity of mono-sensitive patients with rhinitis in the southern Mediterranean area, in relation to skin reactivity to allergens, total serum IgE levels and blood eosinophils. OBJECTIVES: The significance of the association between allergic rhinitis, and abnormal airway responsiveness with regard to the pathogenesis of asthma is unclear. For this reason, we have studied non-specific bronchial hyperreactivity, in patients with seasonal allergic rhinitis, with reference to the responsible allergen. The aim of the study was to correlate the responsiveness to bronchoprovocation with methacholine in subjects a with allergic rhinitis during and out of the pollen season with total serum IgE and blood eosinophils. METHODS: Fourty-nine non-smoking patients with clinical diagnosis of allergic rhinitis and mono-sensitive skin-prick tests to pollen allergens were enrolled in the study. Twenty patients suffered from seasonal rhinitis to Parietaria pollen, 15 patients to Gramineae pollen and 14 patients to Olea pollen. In all patients lung function measurements (assessed as response to methacholine), total serum IgE and blood eosinophil counts were measured during and out of the pollen season. RESULTS: During pollen season, 16 out of 49 rhinitis patients demonstrated values of bronchial responsiveness measured as response to inhaled methacholine in the asthmatic range whereas out of the pollen season only eight patients were in the asthmatic range. By analysing the results with reference to the responsible allergen, during the pollen season 15 out of 16 patients were Parietaria-sensitive and out of the pollen season seven out of eight patients. Finally, in Parietaria-sensitive rhinitis bronchial responsiveness significantly correlated, during and out of the pollen season, with total serum IgE and with blood eosinophil counts. CONCLUSIONS: Our results are consistent with the hypothesis that Parietaria is more important than Olea and Gramineae as a risk for developing non-specific bronchial hyperresponsiveness. On the whole, present observations provide further evidence that there is an interrelationship of allergen kind, total serum IgE, eosinophil and bronchial hyperresponsiveness suggesting that they may play a role in the development of bronchial asthma in rhinitis patients.

Adult↗
PubMed1997

HLA-B8,DR3 haplotype affects lymphocyte blood levels.

The number of lymphocytes in the blood is constant, pointing to an effective control of circulating lymphocyte values. The mechanisms of this regulation are uncertain, although it is likely that the number of blood lymphocytes is conditioned by hormones, homing factors and cytokines whose production is at least partly restrained by genetic factors. Particularly genetic factors linked to major histocompatibility complex (MHC) appear to be involved. In human beings a decreased number of blood lymphocytes has been described in healthy subjects carrying the Human Leucocyte Antigens (HLA) haplotype HLA-B8,DR3. In the present study, to inquire into the mechanisms of this lymphocyte decreased number, we have performed an analysis of blood subset values in these subjects. When the absolute values of lymphocytes were analysed according to HLA phenotype, HLA-B8,DR3 positive subjects (N = 26) displayed significantly lower values as compared to HLA-B8,DR3 negative ones (N = 282). The analysis of lymphocyte subpopulations performed by flow cytometry in 72 subjects did not show significant changes in lymphocyte subset percentages between HLA-B8,DR3 positive subjects and negative ones. Thus, the decrease of circulating lymphocytes seems to be due to a reduction of cell number affecting all lymphocyte subsets rather than a single cell subpopulation. The analysis of in vitro spontaneous apoptosis performed by flow cytometry in a smaller sample of subjects showed a significant increase of spontaneous apoptosis in lymphocytes from HLA-B8,DR3 positive individuals suggesting a possible explanation for the deviation from normal lymphocyte count observed in these subjects. However it is intriguing that a decreased number of blood lymphocytes can be observed in healthy HLA-B8,DR3 positive subjects but also in autoimmune diseases linked to this haplotype like systemic lupus erythematosus and insulin-dependent diabetes. Furthermore, in our opinion, this finding is to be kept in mind in evaluating hematological parameters in healthy subjects.

Adult↗
PubMed1997

Phenoloxidase-dependent cytotoxic mechanism in ascidian (Styela plicata) hemocytes active against erythrocytes and K562 tumor cells.

The cytotoxic activity against rabbit erythrocytes (RE) and human K562 tumor cells by Styela plicata hemocytes was significantly related to the phenoloxidase (PO) which converts phenols to quinone and initiates the melanogenic pathway. The effector hemocyte population, separated in a Percoll density gradient band, enriched in a granulocyte type named "morula cells", was examined with RE in a hemocyte cytotoxic assay and plaque forming cell assay. Inhibition experiments with the copper chelating agents 1-phenyl-2-thiourea and tropolone, the substrate analogue sodium benzoate and sodium ascorbate support the notion that hemocyte cytotoxic activity is a PO-dependent mechanism. Treatments of hemocytes with the antioxidant enzymes, superoxide dismutase and catalase rule out oxy radicals produced by the melanogenic process as responsible of erythrolysis. Such a result suggests that quinone compounds derived from the melanogenic pathway might be the cytotoxic molecules. The PO-dependent anti-RE activity was also shown in a plaque forming assay in which "morula cells", containing polyphenols and PO, were identified as cytotoxic.

Animals↗
PubMed1997

Modification of cytokine patterns in subjects bearing the HLA-B8,DR3 phenotype: implications for autoimmunity.

The factors influencing the pathogenesis of autoimmune disease are not fully known, but the host genotype undoubtedly plays a role in determining the outcome of these diseases. The role of the host's major histocompatibility complex (MHC) genotype in the regulation of susceptibility to autoimmune diseases has been extensively studied in different populations, and certain HLA (the human MHC) alleles and haplotypes have been reported to be associated with several autoimmune diseases. In particular, the association with genes from the HLA-B8,DR3 haplotype has been reported by different research groups. This haplotype is associated in all Caucasian populations with a wide variety of diseases with autoimmune features, and in healthy subjects it is associated with a number of immune system dysfunctions. Mainly, peripheral blood mononuclear cells from HLA-B8,DR3-positive and -negative individuals differ in their ability to produce interleukin (IL)-2, IL-5, IL-12 and interferon-gamma upon stimulation with the mitogen phytohaemoagglutinin (PHA), while producing similar amounts of IL4, IL-6 and IL-10. Furthermore, in HLA-B8,DR3-positive subjects tumor necrosis factor alpha secretion is increased both with and without PHA stimulation. Accurate control of the functional repertoire of an immune response is a critical parameter in the response to infections as well as in immunopathology. MHC control of the class of the immune response at the level of cytokine production is a sophisticated way in which this occurs. This control might be involved in adaptive immune responses to infections as well as in immunopathology.

Animals↗
PubMed1996

In vitro T cell activation in elderly individuals: failure in CD69 and CD71 expression.

A large number of T cell dysfunctions have been observed in the elderly. The most widely observed is the inability of these cells to proliferate at a level comparable to T cells from young individuals after stimulation by mitogens. To better characterize T cell impairment, we have focused on the in vitro T cell activation, analyzing by flow cytometry the activation molecules CD69 and CD71 on mitogen-stimulated lymphocytes from young and elderly subjects. The results show that the percentages of CD69+ and CD71 + T cells were significantly decreased in cultures from elderly subjects when compared to values obtained culturing cells from young individuals. The differences observed seem not due to differences in CD4 and CD8 rates in the "old' cells that underwent activation, since, following activation, the pattern of CD4 and CD8 phenotypes was the same in both groups of subjects. Signals from CD69 are relevant in controlling cytokine gene expression because its stimulation leads to interleukin-2 production and increases its receptor expression. The interaction of this cytokine with its cellular receptor is an essential requirement for T lymphocytes to express CD71 and to start proliferation. Thus, a key role in the age-associated impairment of T cell activation could be played by an ineffective modulation of CD69 expression suggesting a defect in the signal transduction pathway of the T cell receptor-CD3 complex in elderly.

Adult↗
PubMed1996

Cytokine production pathway in the elderly.

It is well known that aging is associated with various alterations in lymphoid cell functions, particularly with a progressive decline in immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena. Many studies have been focused on the mechanisms of the immunologic features of aging. this review describes our results of studies performed to determine the influence of age on the capacity to produce interleukin-2 (IL-2), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-t (IL-5), interleukin-6 (IL-6) and tumor necrosis factor (TNF). Mitogen-stimulated cultures of mononuclear cells (MNC) from human beings were assessed for cytokine-producing capacity. A significant decrease in IFN-gamma and IL-2 production by MNC cultures from elderly individuals was observed. No significant difference was instead observed between cultures from elderly individuals and those from young ones as regards TNF-alpha, IL-4 and IL-6 production. Mitogen or antigen-stimulated cultures of MNC from aged mice also displayed a significant decrease in IFN-gamma and IL-2 production as well as TNF-beta. Instead IL-4 and IL-5 production significantly increased in these cultures. We suggest that this imbalanced cytokine production may well account for the pattern of immune response which may be observed in the elderly, i.e. a normal or increased humoral response (including autoimmune responses) in face of a low T cell immune responsiveness.

Aged↗