The importance of the nurse cells and regulatory cells in the control of T lymphocyte responses.

T lymphocytes from the immune system are bone marrow-derived cells whose development and activities are carefully supervised by two sets of accessory cells. In the thymus, the immature young T lymphocytes are engulfed by epithelial "nurse cells" and retained in vacuoles, where most of them (95%) are negatively selected and removed when they have an incomplete development or express high affinity autoreactive receptors. The mature T lymphocytes that survive to this selection process leave the thymus and are controlled in the periphery by another subpopulation of accessory cells called "regulatory cells," which reduce any excessive immune response and the risk of collateral injuries to healthy tissues. By different times and procedures, nurse cells and regulatory cells control both the development and the functions of T lymphocyte subpopulations. Disorders in the T lymphocytes development and migration have been observed in some parasitic diseases, which disrupt the thymic microenvironment of nurse cells. In other cases, parasites stimulate rather than depress the functions of regulatory T cells decreasing T-mediated host damages. This paper is a short review regarding some features of these accessory cells and their main interactions with T immature and mature lymphocytes. The modulatory role that neurotransmitters and hormones play in these interactions is also revised.

A neurotransmitter system that regulates macrophage pro-inflammatory functions.

Neurotransmitters released through peripheral and autonomic nerves play an important role in the signaling from the cells of the nervous system to lymphocytes, macrophages and other cells of the immune system. Macrophages are related to numerous physiological and pathological inflammatory processes since their cytokines play an important role in the defensive responses against invasive microorganisms, atherosclerosis progress, insulin resistance, behavior deviation, hematopoiesis feedback, degenerative chronic diseases and the stimulation of the hypothalamus-hypophysis-adrenal axis. Production of pro-inflammatory cytokines by macrophages is the main target for the modulatory activity of diverse neurotransmitters. In this brief review, we show how some neurotransmitters released by the central or the autonomic nervous systems down-regulate peripheral macrophages' inflammatory functions to balance immune protective mechanisms, although they can also promote the collateral progress of diverse diseases. The possible therapeutic uses of some neurotransmitters and the agonists or antagonist of their respective receptors are included as well.

GABA (A) receptor subunits RNA expression in mice peritoneal macrophages modulate their IL-6/IL-12 production.

The expression and functionality of the gamma aminobutyric acid A receptor (GABA(A)R) in mice macrophages was explored. Reverse Transcriptase-Polymerase Chain Reaction showed that macrophages express the GABA(A)R RNA for the alpha1, alpha2, beta3 and delta subunits, but not for the alpha5, beta1, beta2 and gamma3 subunits. The expression of alpha1 subunit was also revealed by confocal microscopy. LPS-stimulated macrophages significantly reduced their in vitro production of IL-6 and IL-12 after GABA adding to the culture medium. These results showed that BALB/c mice peritoneal macrophages express a functional subset of GABA(A)R subunits.

Stressful stimulation of newborn mice increases the in vitro proliferative response in T cells from thymus

The effects of prolonged stressful stimulaton on the in vitro proliferative response of thymic T cells and the thymic zinc concentration were investigated in newborn Balb/c mice. Animals were stressed y intraperitoneal injections with aliquots from a heat-killed staphyloccocal suspension over one month. The splenic T lymphocytes from the stressed animals showed a significant reduction in the in vitro response to cancanavalin A (Con-A) stimulation. However, an unexpected and significant increase in proliferative response was observed when thymic lymphocytes from stressed animals were stimulated with the same mitogen. The intrathymic zinc levels were regularly elevated in stressed mice, in contrast to those values obtained in the thymus from healthy control mice. These results suggest that neonatal stress can disrupt the intrathymic maturation and the selection of pre-T lymphocytes. The increment of the in vitro proliferative response of T cells from of thymus of stressed mice may be caused by proportionally higher amounts of intrathymic lymphoid suppopulations expressing a mature phenotype and functionality

Bacterial translocation and wasting in stressed mice

The effects of strees immunity and on the bacterial translocation from intestine to mesenteric lymph nodes, liver, and spleen were studied in a group of newborn CD1 mice. Animals were separated into three experimental groups. Mice from group I were stressed by intraperitoneal (IP) injections of heatkilled staphylococci for 4 weeks. Mice from group II were IP injected with saline solution only. The remaining mice, group III, were not injected. The clinical condition, presence of bacteria in abdominal organs, mitochondrial activity in splenic cells, lymphocyte proliferative response to Concanavalin-A and in vitro antibody production were evaluated in each mouse. Results showed that prolonged IP stressor challenge causes severe weight loss and immunodeficiency. The splenic lymphocytes from stressed mice exhibited a significant depression of both proliferative response to Concanavalin-A stimulation and anti-erythrocytes antibody synthesis. Instead, cultured in basal conditions, the splenic cells from stressed mice have an increased capacity to reduce the tetrazolium salts. Bacterial dissemination from intestine to mesenteric lymphoid nodes was also confirmed in the same group of mice. In contrast, mice in groups II and III presented no weight loss and immunodeficiency. Results suggest that chronic biological stress induced in newborn mice could facilitate the translocation of Gramnegative bacteria. Probable pathogenic mechanisms are commented upon and a correlation is proposed between the bacterial dissemination and the wasting development

Zinc administration prevents wasting in stressed mice

Experimentally induced chronic stress can produce severe retardation on the physical development of young animals. Moreover, the chronic stress and its associated secondary malnutrition cause a variable depression on immunity, whose pathogenesis has been related to the excessive production of cytokines and glucocorticoids. When stressful stimuli are excessive, animals increment their anorexia and express a progressively installed wasting syndrome, associated with hypozincemia and susceptibility to infections with high mortality rate. In this work, chronically stressed mice were studied to observe the prophylactic effect of a zinc treatment on the evolution of both their malnutrition and their immune competence. Stress was induced in newborn Balb/c mice by intraperitoneal (IP) injections with heat-killed bacteria for 4 weeks. Following this inductive period, almost all the stressed mice showed a transient wasting syndrome characterized by anorexia, deficient gain of corporal weight, diarrhea, skin infection, reduced antibody response against antigens of red blood sheep cells, and a decreased proliferative response in their Con-A stimulated splenic lymphocytes. However, when the stressed mice received an additional IP treatment with zinc acetate, their clinical condition showed a significant improvement and their immunocompetence was similar to that exhibited by non-stressed mice fron the control groups. The results suggest that zinc supplementation can ameliorate the effects of chronic stress on the growth, corporal weight, and immunocompetence of young mice

La inmunodeficiencia experimental del animal desgastado y/o desnutrido / Experimental inmunodeficiency of wasted animals and/or undernourished

En este trabajo se estudia la competencia inmunológica en un grupo de ratones recién nacidos, a los cuales se les indujo una inmunodeficiencia, secundaria mediante la inoculación intraperitoneal de estafilococos muertos. Los ratones fueron divididos en varios grupos para estudiar la producción de anticuerpos, la inducción de una reacción local injerto-contra-huésped (GvH) y la tolerancia inmunológica oral. Los resultados mostraron que los ratones inyectados con estafilococos tenían deprimida la producción de anticuerpos y una incapacidad para desarrollar tolerancia oral, sin cambios significativos de la respuesta in vivo contra antígenos alogénicos. Todos los ratones inoculados detuvieron su desarrollo y, al final del primer mes de vida, estaban desnutridos con un peso promedio 40% menos que el de controles sanos. La interacción con los estafilococos comprometió tanto a la inmunidad sistémica como la de la mucosa intestinal. Este trastorno inmunológico difiere del que tienen los animales desnutridos debido a una dieta deficiente en proteínas y calorías. La enfermedad del desgaste se ha considerado como una inmunodeficiencia animal selectiva y transitoria que puede ayudar a explorar el daño inmunológico que causan las infecciones en el niño.

Antígenos de enterobacterias y el tejido linfoide de ratas / Enterobacteriaceae antigens and lymphoid tissue of rats

Por medio de un grandiente de Ficoll-Hypaque se obtuvieron los linfocitos del bazo de 15 ratas Wistar adultas. Con estas células se procedió a preparar 15 extractos solubles en etanol al 85%, los cuales fueron ajustados posteriormente a 1.5 mg/mL y utilizados para inhibir una prueba de fijación del complemento. Para esta reación se utilizó un sistema antígeno-anticuerpo heterólogo que sólo revelaba la presencia de antígenos omunes a todas las enterobacterias. Los 15 extractos de tejido linfoide esplénico inhibieron la reación. Las unidades de complemento inhibidas fueron convertidas en microng/mL de antígenos comunes a las fracciones de enterobacterias que eran solubles en etanol. Por cada 1.5 mg/mL de extracto de linfocitos esplénicos se encontraron 10-50 microng/mL de antígenos compartidos con las enterobacterias. Los resultados están en favor de la absorción contínua de residuos lipopolisacarídicos derivados de las bacterias gramnegativas del intestino y, además, apoyan el concepto de que estas substancias se ligan a la membrana de los linfocitos y probablemente participan en la modulación de sus funciones