Lymphocyte subpopulations in sensitization and specific immunotherapy in an experiment. Lymphocyte subpopulations in sensitization to staphylococci, Artemisia pollen and their combinations

The distribution of T- and B-lymphocytes in the body of guinea pigs was studied in different groups of the animals. As shown in this study, in delayed hypersensitivity to staphylococci the number of PE- and E-rosette-forming cells increased in the blood, the spleen, and the lymph nodes and decreased in the thymus; the number of EA- and EAC-rosette-forming cells decreased in the bone marrow and the spleen, the number of T gamma-suppressors decreased in the bone marrow and the distant lymph node. Immediate hypersensitivity to tarragon pollen induced the general increase of the content of T- and B-lymphocytes; the number of T gamma-cells decreased in the thymus, the bone marrow, and the lymph nodes and increased in the spleen. The characteristic features of combined microbial-pollen sensitization were the high content of B-cells in all lymphoid organs (except the thymus), a low level of T-lymphocytes in the blood and the peripheral lymphoid organs, the decreased number of T gamma-cells in most of the immunogenetic organs.     

Imbalances of T cell subpopulations in patients with atopic diseases and effect of specific immunotherapy.

Reduced numbers of T cells with Fc receptors for IgG (TG cells) are present in blood samples of patients with respiratory allergic disease, mainly those with severe symptoms. TG cells have been previously shown to be suppressor in the pokeweed mitogen- (PWM) dependent B cell differentiation. T cells with Fc receptor for IgM (TM cells), which help immunoglobulin production, are in a normal range. After specific hyposensitization, resulting in a sharp improvement of clinical symptoms, TG cell subset reached normal values.     

Lymphocyte subpopulations and cytokine production in paracoccidioidomycosis patients.

Despite the postulated role of the immune system in the control of the infection by Paracoccidioides brasiliensis, only a few studies have addressed this point in patients. The determination of total lymphocytes and their subpopulations in 6 untreated patients with the chronic form of paracoccidiodomycosis showed that half of them were lymphopenic, because of low number of CD4+ T-lymphocytes. All patients had low CD4/CD8 ratios. On the contrary, B-lymphocytes were normal in all patients. An additional patient, studied on treatment with ketoconazole, had normal lymphocyte counts in all subpopulations, as did one of the patients previously studied at diagnosis when he received specific antimycotic treatment. The production of interferon and tumor necrosis factor, determined by bioassay in supernatants of mononuclear blood cells of the patients, induced by interleukin 2 in vitro was significantly lower than that of normal subjects. These results show that patients with paracoccidioidomycosis have a defect in blood lymphocyte subsets as well as in the ability to produce regulatory cytokines.     

The relationship between airborne pollen distribution and the frequency of specific pollen sensitization at two climatically different locations in Switzerland

Pollen data reported from the two monitoring stations of Locarno-Monti, on the southern slopes of the Alps, and Zurich on the northern slopes of the Alps, for the years 1989–1993 were compared with meteorological data from the corresponding locations and with the prevalence of pollinosis and frequency of specific pollen sensitization in patients with pollinosis. It was so discovered that the recorded quantity of allergenic pollen types (Alnus, Corylus, Betula, Fraxinus, Poaceae, Castaneae,Olea andArtemisia) south of the Alps is higher by a factor of 2.9 than that north of the Alps. These differences are due to the distinctly milder climate in the canton of Ticino (south of the Alps) showing higher annual mean temperatures, more sunshine duration and less precipitation days with higher amounts of precipitation. The allergological data show additionally that the summer pollinosis, caused byCastanea andOlea, is probably responsible for the differing prevalence of pollinosis at the two sites. Finally, we can summarize that in Switzerland pollen from Poaceae, Betulaceae and Oleacea are the most important for pollinosis.     

Costimulation blockade inhibits allergic sensitization but does not affect established allergy in a murine model of grass pollen allergy

Type I allergy is characterized by the development of an initial Th2-dependent allergen-specific IgE response, which is boosted upon a subsequent allergen encounter. Although the immediate symptoms of allergy are mainly IgE-mediated, allergen-specific T cell responses contribute to the late phase as well as to the chronic manifestations of allergy. This study investigates the potential of costimulation blockade with CTLA4Ig and an anti-CD154 mAb for modifying the allergic immune response to the major timothy grass pollen allergen Phl p 5 in a mouse model. BALB/c mice were treated with the costimulation blockers at the time of primary sensitization to the Phl p 5 allergen or at the time of a secondary allergen challenge. Costimulation blockade (CTLA4Ig plus anti-CD154 or anti-CD154 alone) at the time of sensitization prevented the development of allergen-specific IgE, IgM, IgG, and IgA responses compared with untreated but sensitized mice. However, costimulation blockade had no influence on established IgE responses in sensitized mice. Immediate-type reactions as analyzed by a rat basophil leukemia cell mediator release assay were only suppressed by early treatment but not by a costimulation blockade after sensitization. CTLA4Ig given alone failed to suppress both the primary and the secondary allergen-specific Ab responses. Allergen-specific T cell activation was suppressed in mice by early as well as by a late costimulation blockade, suggesting that IgE responses in sensitized mice are independent of T cell help. Our results indicate that T cell suppression alone without active immune regulation or a shifting of the Th2/Th1 balance is not sufficient for the treatment of established IgE responses in an allergy.     

Formation of pollen-induced allergy in guinea pigs after specific immunotherapy with a bacterial allergen

The investigation was aimed at elucidating the process of the development of allergy to exoallergens (e.g., to linear-leaf wormwood pollen) in the body after desensitization by specific immunotherapy (SIT) with heterologous (staphylococcal) allergen. The study revealed that in staphylococcal allergy the subsequent development of pollen sensitization occurred with greater intensity, and SIT was found to exert no influence on this process. For the first time pollen allergy was found to produce an unfavorable effect on the quality and effectiveness of SIT with heterologous staphylococcal allergen, this effect consisting in the acceleration and intensification of the process leading to the recovery of sensitization to staphylococci. The importance of measures for limiting contacts with heterologous allergens and their elimination during SIT is emphasized.     

Mathematical modeling of allergy and specific immunotherapy: Th1-Th2-Treg interactions

Regulatory T cells (Treg) have recently been identified as playing a central role in the immune response to allergens and during allergen-specific immunotherapy. We have extended our previous mathematical model describing the nonlinear dynamics of Th1-Th2 regulation by including Treg cells and their major cytokines. We hypothesize that immunotherapy mainly acts on the T cell level and that the decisive process can be regarded as a dynamical phenomenon. The model consists of nonlinear differential equations which describe the proliferation and mutual suppression of different T cell subsets. The old version of the model was based upon the Th1-Th2 paradigm and is successful in describing the “Th1-Th2 switch” which was considered to be the decisive event during specific immunotherapy. In recent years, however, the Th1-Th2 paradigm has been questioned and therefore, we have investigated a modified model in order to account for the influence of a regulatory T cell type. We examined the extended model by means of numerical simulations and analytical methods. As the modified model is more complex, we had to develop new methods to portray its characteristics. The concept of stable manifolds of fixed points of a stroboscobic map turned out to be especially important. We found that when including regulatory T cells, our model can describe the events in allergen-specific immunotherapy more accurately. Our results suggest that the decisive effect of immunotherapy, the increased proliferation of Treg and suppression of Th2 cells, crucially depends on the administration of high dose injections in short intervals right before the maintenance phase sets in. Empirical protocols could therefore be improved by optimizing this step of therapy.     

Lymphocyte subpopulations in Lynch syndrome II: an immunocytochemical study on gastrointestinal biopsies. Preliminary report

Gastrointestinal biopsies from 18 members of a family with Lynch Syndrome II were evaluated and immunocytochemical studies were made to characterize the phenotypic expression of the tissue's immune populations. The intestinal findings suggest polyclonal B-cell activation related to the T-helper distribution. Our evaluation provides no specific information so far on the management of patients with Lynch Syndrome II.     

Lymphocyte subpopulations and the expression of intercellular adhesion molecules in chronic periodontitis

Immunological responses to invading bacteria play a major role in the course of inflammatory periodontal diseases, such as CP. It was suggested that one of the major elements in determining the course of the disease is the expression of cellular adhesion molecules. We therefore investigated the expression of cellular adhesion molecules, ICAM-1 and beta-1 integrins, capillary density and lymphocyte subpopulations in gingival biopsies obtained from 20 patients with CP who responded and 21 patient who failed to respond to initial treatment using immunohistochemical methods. We found no differences between the two groups in capillary density, ICAM-1 and beta-1 integrin expression. Patients who responded to treatment had a lymphocytic inflammatory infiltrate consisting predominantly of T cells, while those who failed to respond had an approximately equal number of T and B cells. Our findings support the role of host immunological mechanisms in determining the outcome of CP and argue against a major role of differential cellular adhesion molecule expression.     

The effect of heterologous bacilli on the infectious process in anthrax in an experiment

The possibility of the survival of guinea pigs after the simultaneous administration of different doses of Bacillus anthracis virulent strain 81/1 in combination with both B. anthracis vaccine strain STI and heterologous bacilli (B. subtilis strain PAC) has been experimentally shown. On the basis of the results of these experiments suggestion has been made that the "survival phenomenon" is the process involving the lysosomal systems of polymorphonuclear and mononuclear phagocytes.     

Lymphocyte subpopulations and function in chronic murine toxoplasmosis. II. Cyclic immunosuppression in genetic-low-responder mice

Cyclic unresponsiveness to a bacterial antigen was caused by chronic infection with Toxoplasma gondii in genetic-low-responder mice but not in a high-responder strain. No direct correlation was found between unresponsiveness and the gradual lymphoid cell depletion that accompanies chronic toxoplasmosis.     

Lymphocyte subpopulations, cytokines and trace elements in asymptomatic atopic women exposed to an urban environment

This study evaluates the immune response to exposure to an urban environment from 30 non-atopic and 30 non-symptomatic women with history of respiratory and/or cutaneous allergies. Blood lymphocyte subsets and serum interleukin (IL) 4 and interferon gamma (INF-gamma) of the two groups were similar, while serum IgE and "in vitro" production of IL-4 and INF-gamma by mononuclear blood cells of the atopic women were higher spontaneously or in the presence of PHA, respectively. Blood lead of the nonatopic women (mean 55 microg/l) was positively correlated with CD4+-CD45RO-, CD3+-CD8+ and CD3--HLA-DR+ lymphocyte subsets, while urinary trans-trans muconic acid (a metabolite of benzene) of both groups of women (mean about 50 microg/l) was significantly correlated with NK CD16+CD56+ lymphocytes. Urine chromium of the non-atopic subjects was significantly correlated with activated T, B and NK HLA-DR+ cells. Urine nickel of both groups of women was correlated with CD4+-CD45RO+ "memory" lymphocytes and their ratio with CD4+-CD45RO- "virgin" lymphocytes suggesting that the metal enhances maturation of "virgin" into "memory" lymphocytes. On the whole, this study demonstrates that exposure to low levels of toxic agents, produced by vehicular traffic in an urban environment, exerts effects on immune functions of women.     

Lymphocyte sensitization in sheep inoculated with extracts of spontaneously occurring malignant lymphomas.

A macrophage migration inhibition test showed that the blood lymphocytes of 15 of 27 sheep inoculated in utero or at birth with disrupted cells from ovine malignant lymphomas responded in culture to antigens derived from three other lymphomas. A close association was seen between animals whose lymphocytes were antigen-sensitive and those which developed lymphocytosis. This association and the specificity of reaction between the various tumour antigens employed in the tests is interpreted as further evidence toward a viral aetiology in ovine malignant lymphoma.     

Lymphocyte subpopulations in malignant ascites of serous papillary ovarian adenocarcinoma. An immunocytochemical study

The aim of this study was to investigate lymphocyte subpopulations in 17 patients with malignant ascites due to serous papillary adenocarcinoma of the ovary. Eight patients had not been treated prior to the study whereas nine patients had been treated by surgery and chemotherapy. A panel of monoclonal antibodies against surface markers that correlate with the immune functions of the lymphocytes was used. The lymphocyte subpopulations were identified by the immunoperoxidase adhesive slide assay, and the results in treated and untreated patients were compared. Both groups of patients showed lymphocytosis (41 +/- 25% and 33 +/- 14% of the total cells, respectively). The untreated patients had a significantly higher proportion of B cells (14 +/- 4% of lymphocytes) than did treated patients (7 +/- 2%). No differences were found between both groups regarding the helper-inducer/suppressor-cytotoxic T lymphocyte ratio. The proportion of lymphocytes expressing interleukin-2-receptors was higher in treated patients (6 +/- 2%) than in untreated patients (1.2 +/- 1%). Both groups showed a high percentage of natural killer/cytotoxic cells (17 +/- 7% and 18 +/- 5%, respectively). In the only chylous effusion in this study, there was an increase in helper-inducer and activated T lymphocytes. Future studies are required to document whether surface marker analysis of lymphocytes in malignant effusions may be useful for assessment of the prognosis and the results of treatment.     

Lymphocyte subpopulations of regional lymph nodes in human colon and gastric adenocarcinomas

 In order to study the host immune response to tumours, previous knowledge of the cellular composition of regional draining lymph nodes is necessary. Enlarged regional lymph nodes are a common finding in colon and gastric adenocarcinomas. We have studied the cellular composition of normal non-reactive and of regional draining lymph nodes of colon and gastric adenocarcinomas. In normal non-reactive lymph nodes, T lymphocytes (CD2⁺, CD7⁺) constituted the largest fraction of the lymphoreticular cells. These lymphocytes were mainly CD4⁺, and there were more cells expressing the CD45RA isoform of the CD45 antigen than CD45RO. Reactive lymph nodes presented a decreased proportion of CD4⁺ CD45RA⁺ cells and an increased number of B cells. Although most of the T cells in the reactive nodes were CD4⁺ CD45RO⁺, their proportion was similar to that found in normal non-reactive nodes. We studied the presence of the molecules CD28 and CD80 involved in the processes of interaction and activation of T and B lymphocytes. The CD28 molecule was found in all the T lymphocytes, while the CD80 molecule was weakly expressed on the B lymphocyte membrane. Received: 4 January 1996 / Accepted: 28 May 1996     

Cellular immunity to heterologous erythrocytes in vitro. I. The role of surface-adherent cells and specific mediators in an effector mechanism

An in vitro assay measuring spleen cell-mediated destruction of heterologous erythrocytes has been developed. The assay is immunospecific, complement independent, and requires both antibody-releasing and surface-adherent cells. An immunoglobulin-like mediator is released as a part of the reaction. This mediator is apparently produced (or released) by nonadherent cells and interacts with surface-adherent cells to accomplish specific target cell lysis.