The literature concerning the autologous mixed lymphocyte reactions has been reviewed. This analysis supports the following conclusions: human subjects have self-responsive cells which are capable of proliferating when co-cultured with irradiated autologous non-T or Ia+ T cells. Since monoclonal antibodies recognizing distinct determinants of Ia antigen have different effects on AMLR with non-T cells and on Ia+ type AMLR, there is the possibility that different Ia molecule determinants have different functional role in the process of cell-to-cell interaction. The presence of AMLR abnormalities in disease strongly suggests that reactivity among different cell subsets plays a role in immunological homeostasis.

Animals↗

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Quantitative analyses of plasma opsonizing activity and polymorphonuclear cell response during phagocytosis: standardisation of a chemiluminescent method.

Although measurement of chemiluminescence has become a widespread tool in the study of phagocytosis of peripheral neutrophils, several problems linked to spontaneous fluctuation in chemiluminescence and the number of variables involved have occasionally either limited its usefulness for clinical and experimental purposes or compelled operators to take particular care when using the technique. In the present paper, sources of variability are investigated and most of the parameters involved are thoroughly analysed and step-by-step normalised. A stochastic calibration procedure for validation of the method is applied and a monofunctional test protocol for quantitative evaluation of plasma opsonizing activity in whole blood chemiluminescence is suggested. With regard to the goal of proposing a reverse monofunctional test, we discuss the reasons why further studies aimed at standardised evaluation of the cellular components are needed.

Adult↗

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The effect of aging on host defences. Implications for therapy.

Immunosenescence is a well known physiological phenomenon resulting from reduced efficiency of the immune system in the elderly. It has been studied both in animal models and in humans. In this review attention is focused on T cell responsiveness, since this cell type is both a marker of the immune response and one of the main targets of several drugs. For this latter reason, most studies of the effect of drugs on the immune system have been performed with reference to the effects on T lymphocytes. In the second part of the article experimental data concerning several drugs and drug classes [steroids, calcium antagonists, theophylline, histamine H1- and H2-receptor antagonists, sodium cromoglycate (cromolyn sodium), pirenzepine, rosaprostol, beta 2-mimetics, antibiotics and antibacterials] and immune responsiveness are reviewed. Lastly, the clinical perspectives of pharmacological treatment in aged subjects in relation to immunosenescence are evaluated.

Aged↗

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[A case of type II congenital dyserythropoietic anemia. Clinico-hematologic and anatomo-histological study].

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Adolescent↗

PubMedDate not supplied

Hepatitis C virus and autoimmune manifestations.

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Autoantibodies↗

PubMedDate not supplied

Decreased surface antigen density on lymphocytes of elderly humans.

The aim of our study was to analyze some poorly investigated and controversial aspects of senescent lymphocyte phenotype and functions. We examined 100 healthy aging individuals, divided into 4 age groups, and 30 young controls, correlating lymphocyte responsiveness to mitogenic stimulation with membrane phenotypic pattern and surface molecular densities of the main functional lymphoid markers. Stability of values in the period of study was established. No age-related differences in the parameters evaluated were detected among aging subjects. Phytohemagglutinin-induced lymphocyte proliferation was found severely impaired (about halved) in all elderly individuals with respect to controls. There was no significant difference between elderly group and controls in CD2, CD3, CD4, CD8, CD19, CD25 and HLA-DR antigen distribution. CD56 positive cell percentages were slightly decreased in the elderly groups. In apparent correlation with reduced lymphocyte responsiveness, CD2, CD3, CD4 and CD8 molecular densities, to different extents, were found relevantly (about 1 to 3-fold) lower in all aging groups than in controls. We could not ascertain if those antigens were poorly synthesized, defectively transported to membrane or shed in excess. However, we suggest that decreased surface molecular densities of antigens involved in functional processes of immune responses may be responsible for an abnormal costimulatory pattern during lymphocyte activation, leading to apoptotic rather than proliferative signals in a greater proportion of cells than normal.

Age Factors↗

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[The immunomodulatory effect of blood transfusions and intravenous immunoglobulins: the role of the soluble molecules of the Class-I major histocompatibility complex and of the Fas ligand].

Allogeneic blood transfusions may have immunomodulatory effects including improved allograft acceptance and increased risk for cancer recurrence or post-operative bacterial infections. These effects are associated with the presence of leukocytes in transfused blood and are reduced by pre-storage leuko-reduction. However, the precise mechanism of this effect has not yet been elucidated. We report that the concentrations of soluble major histocompatibility complex class I and soluble Fas-ligand molecules are significantly higher in supernatants of blood components containing elevated numbers of residual donor leukocytes, such as red blood cells and random-donor platelets, than in other blood components. Elevated amounts of soluble Fas-ligand molecules are also found in some intravenous immunoglobulin preparations. Soluble molecules detected in blood components and in immunoglobulin preparations are biologically active in vitro. In fact, they inhibit mixed lymphocyte responses and cytotoxic T cell activity in allogeneic and autologous combinations and induce apoptosis in Fas-positive cells. These results should be taken into account in clinical practice to select the blood component or the immunoglobulin preparation in order to induce or prevent an immunosuppressive effect in the recipient.

Adjuvants, Immunologic↗

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Hepatitis G virus infection in intravenous drug users with or without human immunodeficiency virus infection.

BACKGROUND/AIMS: To evaluate the HGV infection prevalence in a group of intravenous drug users with or without human immunodeficiency virus coinfection. METHODOLOGY: We studied 57 patients (48 males and 9 females) who were either previous or still ongoing intravenous drug users. Thirty-seven patients were HIV+ve, 55 patients were anti-HCV+ve and 3 patients were HBsAg chronic carriers. Patient sera were tested for HGV-RNA, anti-E2, qualitative and quantitative HCV-RNA as well as for HCV genotypes. Moreover, the ALT level was checked in the serum sample of each patient. RESULTS: We found a high prevalence (35/57; 61.4%) of HGV infection in our patients. HGV-RNA was detected in 16 out of the 57 intravenous drug users (28%). In particular HGV-RNA was positive in 12 out of the 37 HIV+ve patients (32.4%) and in 4 out of the 20 HIV-ve patients (20%). Anti-E2 were detected in 19 out of the 57 patients (33.3%) with greater prevalence among HIV-ve subjects (12/20; 60%) compared to HIV+ve group (7/37; 18.9%). This resulting difference was statistically significant (P < 0.05). All HGV-RNA+ve/anti-E2+ve patients were anti-HCV/HCV-RNA+ve and none of our patients were anti-E2+ve/HGV-RNA+ve at the same time. Significant differences were not found between HGV-RNA+ve and HGV-RNA-ve patients as far as clinical and virological data are concerned. CONCLUSIONS: The prevalence of HGV infection in intravenous drug users proved to be high especially in the HIV+ve group. Moreover HGV was associated with HCV in all our cases. The actual clinical impact of HGV infection remains unclear since HGV does not seems to influence the biochemical, virological or histological alterations caused by HCV infection.

Adult↗

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Long-term treatment of patients affected by systemic sclerosis with cyclosporin A.

The aims of the present study were: 1) to verify the tolerability of long-term, low-dose treatment of patients affected by systemic sclerosis with cyclosporin A; 2) to analyze the clinical outcome of treated patients in relationship to skin, esophageal, lung, kidney and microvascular organ involvement. Nine patients affected by diffuse systemic sclerosis were treated for periods ranging from 3 to 5 years with cyclosporin A at a dosage of 2.5 mg/kg/day. Cyclosporin A treatment was variably associated or not with treatments for Raynaud's phenomenon (pentoxiphylline, defibrotide, low-dose heparin, prostacyclin analogues) in relationship to the needs of single patients. We report on patient clinical evaluations performed every year and including plicometry, esophageal pH-manometry, pulmonary spirometry, renal duplex Doppler sonography, echocardiography as well as nailfold videocapillaroscopy. The results of single tests were converted into scores. The existence of statistically significant differences between baseline mean scores and mean scores after 1, 2 and 3 years of therapy was analyzed. All patients tolerated cyclosporin A well, and no definitive withdrawals from the study were observed. Hypertricosis appeared in 3 patients, and 1 patient interrupted treatment for 6 months because of the onset of pneumonitis. No alterations of blood pressure and renal functionality were detected. Statistically significant reduction of all analyzed mean scores was observed after 2 and/or 3 years of cyclosporin A treatment with respect to baseline. The overall results suggest an encouraging clinical effect for low-dose, long-term cyclosporin A treatment in systemic sclerosis. Satisfactory tolerability and clinical improvement were observed in all the patients consecutively treated for at least 3 years.

Adult↗

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Sera from AIDS patients inhibit the responsiveness of normal lymphocytes in allogeneic and autologous mixed lymphocyte cultures.

We analyzed the effects of 10 sera from patients with AIDS on the responsiveness of normal lymphocytes in allogeneic and autologous mixed lymphocyte cultures (MLR and AMLR). Results show that all AIDS sera significantly inhibit lymphocyte responsiveness in either MLR or AMLR of non-T/T and T/T type. Experiments performed to asses the effects of heat inactivated sera or sera fractions (obtained by ultracentrifugation on membranes with predetermined pore diameters) on either stimulator or responder cells, showed that the suppressive effects are attributable to heat stable factors with a wide range of molecular weights that act mainly on responder T cells. Present data suggest that circulating factors with inhibitory effects on MLR and AMLR responses can be found in AIDS sera. These factors might contribute to the immunosuppression of AIDS patients.

Acquired Immunodeficiency Syndrome↗

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Proliferation in autologous mixed lymphocyte reactions, expression of HLA-class II antigen and serum immunomodulatory activity in patients with renal insufficiency on chronic dialysis.

The proliferative and stimulatory capacities in allogeneic and autologous mixed lymphocyte reactions were evaluated in 5 patients affected by renal insufficiency undergoing maintenance hemodialysis. The expression of HLA class II antigens and Interleukin 2 production by PHA-activated T cells were also investigated. Furthermore the immunomodulatory effects of uremic serum and serum fractions on mixed lymphocyte reactions performed with lymphocytes from normal subjects were analyzed. The results show that both responsive and stimulatory capacities in allogeneic and autologous mixed lymphocyte reactions of non-T/T and T/T type are clearly impaired. The expression of HLA class II antigens by PHA-activated T cells was reduced whereas the production of Interleukin 2 was normal. The autologous and allogeneic mixed lymphocyte reactions of normal lymphocytes were inhibited by unfractionated uremic serum and by a wide range of serum fractions with different molecular weights. All the above mentioned immune defects were not corrected by the dialytic treatment. The present study extends previous reports concerning the defective immunocompetence associated with chronic renal insufficiency showing that: a) the autologous mixed lymphocyte reactions of both non-T/T and T/T type are impaired; b) the uremic serum contains several factors inhibiting the autologous mixed lymphocyte reactions of normal lymphocytes; c) the chronic hemodialytic treatment does not correct these defects.

Adult↗