Rosette formation by macrophages with adhered T lymphocytes is precluded by inhibitors of antigen processing and presentation

We had previously found in autologous human leukocyte cultures, in which dead neutrophils phagocytosis by macrophages occur, macrophages and T CD4 lymphocytes perform a selective cell-cell interaction showing many figures of either one, two or several T- lymphocytes adhering to a central macrophage were seen. Considering that antigen presentation would be necessary for the formation of these immune synapses, we attempted to block rosette formation (i.e., the formation of macrophage associations with at least three lymphocytes) by interfering with both antigen processing and presentation. Culture samples of autologous leukocytes from 7 healthy donors were subjected to either brefeldin A, chloroquine or to an anti-HLA DR antibody. Rosette formation was significantly inhibited in the treated samples (either with brefeldin A, chloroquine or the anti- HLA DR; ANOVA, p<0.001, as compared with the untreated controls). It is concluded that interference with antigen processing and presentation precludes the formation of these cell-cell interactions.

Rosette formation by macrophages with adhered T lymphocytes is precluded by inhibitors of antigen processing and presentation

We had previously found in autologous human leukocyte cultures, in which dead neutrophils phagocytosis by macrophages occur, macrophages and T CD4 lymphocytes perform a selective cell-cell interaction showing many figures of either one, two or several T- lymphocytes adhering to a central macrophage were seen. Considering that antigen presentation would be necessary for the formation of these immune synapses, we attempted to block rosette formation (i.e., the formation of macrophage associations with at least three lymphocytes) by interfering with both antigen processing and presentation. Culture samples of autologous leukocytes from 7 healthy donors were subjected to either brefeldin A, chloroquine or to an anti-HLA DR antibody. Rosette formation was significantly inhibited in the treated samples (either with brefeldin A, chloroquine or the anti- HLA DR; ANOVA, p<0.001, as compared with the untreated controls). It is concluded that interference with antigen processing and presentation precludes the formation of these cell-cell interactions.(AU)

The tumoricidal effect of Trypanosoma cruzi: its intracellular cycle and the immune response of the host.

Many experimental evidences indicate that infection with Trypanosoma cruzi delays or inhibits the growth of malignant tumors in different strains of mice and in rats. These facts were verified by different workers. Although earlier workers proposed that this effect would be due to a toxin of T. cruzi, most of the accumulated evidences do not agree with such proposal. This present hypothesis agrees with the experimental data and proposes that the liberation of many endocellular antigens by destruction of some cancer cells, infected with T. cruzi, gives rise to an autoimmune response against antigens of analogous cancer cells, which limits or inhibits tumor growth. This point of view is supported by experimental studies on Chagas' disease which showed the role of T. cruzi, to induce autoimmune reactions against target organs of the disease. On the basis of this hypothesis I postulate a new way to stimulate the immune system of the host against cancer.

Autologous rosette formation by human blood monocyte-derived macrophages and lymphocytes.

The formation of rosettes between human blood monocyte-derived macrophages and lymphocytes (MLR) in samples harvested from total leukocyte (TL) cell cultures, was confirmed. Experiments with leukocytes obtained from human blood of healthy individuals (n = 17) and prepared under various conditions, were performed. Cytopreparations of each experiment were used for classical staining procedures or for immunohistochemical methods with monoclonal lymphocyte surface markers. Recently obtained blood leukocytes were unable to form MLR, whereas cultured samples of the same cells started to form MLR 15 hr after culturing. At that time, the number of MLR in pelleted samples was 1.18%, reaching a peak of 15.7% at 120 hr of culturing. In cultured but nonpelleted samples, only a few MLR were formed. With monoclonal antibodies, the lymphocytes forming MLR reacted mainly as CD4 positive and much less as CD8 (the ratio was 18:1). Monocyte-derived macrophages were able to form MLR when they underwent transformation into macrophages. The finding that the lymphocytes involved are T-cells, mainly CD4 positive, suggests that in the cell-cell interaction, macrophages could be presenting antigens to the lymphocytes. Besides, because the highest number of MLR occurred in TL samples, whereas few rosettes were formed in the mononuclear cell samples, the existence of some particular mechanism(s) acting on TL samples is suggested.

[The esophagus in patients with Chagas disease in Córdoba, Argentina. Histologico-immunohistochemical, and evacuation time]. / Estudio de esófago en pacientes chagásicos de Córdoba, Argentina. Histológico-inmunohistoquímico, y de tiempo de evacuación.

UNLABELLED: With the purpose of to establish the status of the oesophagus with respect to chagasic aendemia in subjects of the central rural zone of Argentine, we search the esophagic evacuation duration-time by means of a radiologic standardized test which studied the ingested barium transit as well us the caliber of a given oesophagus. 87 chagasic subjects from rural zones of Cordoba and Santiago del Estero, Argentina, were studied. All had several positive serological test for Chagas' infection. As controls 120 similar studies performed in subjects with negative serological tests for Chagas were considered. Besides, an histopathologic study on samples of oesophagus of four cases of chagasic patients deceased by different causes, and selected at random were performed, regarding the plexus of Auerbach and the muscle layers. RESULTS: 63% of chagasic subjects showed lengthening of esophagic evacuation; 35% of these referred some symptoms of oesophagic disfunctionalism. However, most of the cases corresponded to Group I of the Rezende's classification, that is, with normal caliber of oesophagus with slow transit and retention of barium. Only 3 cases were of group II. The histopathologic study showed diminution of the size and the number of neural structures of the Auerbach plexus as well as of the number of the neurone cells; in all they there were moderate infiltration by T-lymphocytes. In some areas there were replacement of neural structures by fibrosis. CONCLUSIONS: The analysis of results by age groups, showed that abnormal peristalsis of the oesophagus was present since the early ages of chagasic subjects, and affected a growing number in adult and elderly groups. Great megaesophagus were infrequent in these chagasic, suggesting that in the production of Groups III and IV of chagasic megaesophagus, that are frequent in other regions of South America, could intervene other factors.

Estudio de esófago en pacientes chagásicos de Córdoba, Argentina. Histológico-inmunohistoquímico, y de tiempo de evacuación. / [The esophagus in patients with Chagas disease in Córdoba, Argentina. Histologico-immunohistochemical, and evacuation time]

With the purpose of to establish the status of the oesophagus with respect to chagasic aendemia in subjects of the central rural zone of Argentine, we search the esophagic evacuation duration-time by means of a radiologic standardized test which studied the ingested barium transit as well us the caliber of a given oesophagus. 87 chagasic subjects from rural zones of Cordoba and Santiago del Estero, Argentina, were studied. All had several positive serological test for Chagas infection. As controls 120 similar studies performed in subjects with negative serological tests for Chagas were considered. Besides, an histopathologic study on samples of oesophagus of four cases of chagasic patients deceased by different causes, and selected at random were performed, regarding the plexus of Auerbach and the muscle layers. RESULTS: 63

of chagasic subjects showed lengthening of esophagic evacuation; 35

of these referred some symptoms of oesophagic disfunctionalism. However, most of the cases corresponded to Group I of the Rezendes classification, that is, with normal caliber of oesophagus with slow transit and retention of barium. Only 3 cases were of group II. The histopathologic study showed diminution of the size and the number of neural structures of the Auerbach plexus as well as of the number of the neurone cells; in all they there were moderate infiltration by T-lymphocytes. In some areas there were replacement of neural structures by fibrosis. CONCLUSIONS: The analysis of results by age groups, showed that abnormal peristalsis of the oesophagus was present since the early ages of chagasic subjects, and affected a growing number in adult and elderly groups. Great megaesophagus were infrequent in these chagasic, suggesting that in the production of Groups III and IV of chagasic megaesophagus, that are frequent in other regions of South America, could intervene other factors.

Ring-shaped nuclei in human neutrophilic leukocytes of healthy individuals: evidence of their occurrence and characteristics.

In our previous work we found the presence of ring-shaped nuclei in circulating neutrophils of healthy individuals whose nuclei were stained only by means of the Feulgen reaction [1]. In our present work, we performed another study on the blood of 52 healthy human donors and stained their blood films with hematoxylin. In all cases, ring-shaped nuclei were revealed. In this series, the number of this type of nuclei was high: 15.61% +/- SD 7.18%. The ring nuclei of healthy humans had thin segments, such as we have previously found by means of Feulgen method.

Enfermedad de Chagas: persistente produccion de una glicoproteina de linfocitos T en pacientes tratados con agentes anti Trypanosoma cruzi. / Chagas disease: persistent production of a glycoprotein of T-lymphocytes in patients treated with antiTrypanosoma cruzi agents

Alto numero de linfocitos T circulantes en pacientes con enfermedad de Chagas son ricos en una sustancia PAS-positiva citoplasmatica (PASPLS), que reacciona como glicoproteina. En el presente trabajo se demuestra que esa sustancia (PASPLS) esta presente tambien en linfocitos de pacientes chagasicos que fueron tratados con drogas anti Trypanosoma cruzi varios anos antes de este estudio. Se hallo que todos mostraron un alto numero de linfocitos circulantes poseedores de PASPLS, tal como los chagasicos no tratados. La correlacion con otros datos del seguimiento de los pacientes tratados sugiere que la intensa actividad PASPLS-productora descrita como caracteristica de Chagas seria mantenida a traves de memoria inmunologica una vez iniciado el fenomeno. Ademas, se registro un avance o, en ciertos casos, la aparicion de manifestaciones clinicas de Chagas, en varios de los tratados con los agentes anti Trypanosoma cruzi, aunque sus parasitemias se negativizaron en todos y en varios casos desaparecieron ademas los anticuerpos anti Trypanosoma cruzi fijadores del complemento. Se estima que sera de interes ampliar la discusion sobre esas evidencias cuando esten disponibles mas datos sobre el fenomeno de PASPLS-produccion en Chagas