γδ T cell homing to skin and migration to skin-draining lymph nodes is CCR7 independent

In most species, γδ T cells preferentially reside in epithelial tissues like the skin. Lymph duct cannulation experiments in cattle revealed that bovine dermal γδ T cells are able to migrate from the skin to the draining lymph nodes via the afferent lymph. For αβ T cells, it is generally accepted that epithelial and mucosal tissue egress is regulated by expression of the CCR7 chemokine receptor. In this study, we tracked the migratory route of bovine lymph-derived γδ T cells and examined their CCR7 cell surface expression in several compartments along this route. Total lymph cells from afferent and efferent origin were labeled with PKH fluorescent dyes and injected into the bloodstream. PKH(+) cells already reappeared in the afferent lymph after 4 h. The vast majority of the PKH(+) cells retrieved from the afferent lymph were of the WC1(+) γδ T cell phenotype, proving that this PKH(+) γδ T cell subset is able to home to and subsequently exit the skin. PKH(+) γδ T cells from afferent and efferent lymph lack CCR7 surface expression and display high levels of CD62L compared with CD4 T cells, which do express CCR7. Skin homing receptors CCR4 and CCR10 in contrast were transcribed by both CD4 and γδ T cells. Our findings suggest that γδ T cell skin egress and migration into the peripheral lymphatics is CCR7-independent and possibly mediated by CD62L expression.     

Afferent and efferent components of joint position sense; interpretation of kinaesthetic illusion

The present model of joint angle perception is based on the following hypotheses: the perception and control of joint angle are closely interrelated processes; central motor commands are adequately expressed by shifts of an equilibrium point resulting from the interaction of antagonistic muscles and a load; two fundamental commands-reciprocal (r) and coactivative (c) provide for changes in activity of the antagonistic muscle pair. The dependence of joint angle on static muscle torque and r and c commands is derived (Eq. 5). The following principles of joint position sense are formulated: 1) the r component of the efferent copy plays the role of a reference point which shifts during voluntary regulation of muscle state, but remains unchanged during any passive alterations of joint position; 2) muscle afferent signals deliver not absolute but relative information (i.e. measured relatively to the central reference point). These signals turn out to be related to active muscle torque; 3) the nervous system evaluates muscle afferent signals on the basis of a scale determined by the level of coactivation of the antagonistic muscles. Kinaesthetic illusions appear to be due to disruptions in perception of afferent and/or efferent components of position sense. The present model is consistent with all the variety of kinaesthetic illusions observed experimentally. A qualitative neurophysiological schema for joint angle perception is proposed involving efferent copy and information concerning muscle torque delivered by the tendon organ, muscle spindle, and perhaps, articular receptors. It is known that the cerebellum incorporates both afferent and efferent information concerning movement. One may presume that it plays an essential role in position sense.     

Afferent and efferent interfaces of lymph nodes are distinguished by expression of lymphatic endothelial markers and chemokines

BACKGROUND: Lymph nodes (LNs) are important sites of connection between the sampled peripheral tissues, the many cells of the immune system, and the blood. The organization of the interface between the afferent and efferent lymphatic vasculature and LN parenchyma is incompletely understood, and obtaining a better understanding of these tissue microenvironments will contribute to an improved understanding of overall lymphatic function. METHODS AND RESULTS: We used histologic approaches to define the distributions of cells expressing lymphatic endothelial cell (LEC) markers in LNs from healthy, simian immunodeficiency virus (SIV) infected, or Mycobacterium tuberculosis infected cynomolgus macaques. Cells at the afferent and efferent interfaces of LNs from all animals showed differential expression of LEC markers, with podoplanin, Prox-1, and VEGFR3 expressed in both microenvironments, but with LYVE-1 expressed only at the efferent interface. The chemokine CCL20 was uniquely expressed at the afferent interface by cells co-expressing podoplanin, and this expression was increased during SIV or M. tuberculosis infection. In contrast, only a small proportion of cells expressing the CCR7 ligand CCL21 co-expressed podoplanin. Treatment of model LECs with the TLR3 ligand poly(I:C) or gamma-irradiated M. tuberculosis increased production of CCL20 without altering CCL21 or LEC marker expression. CONCLUSIONS: This study provides a comprehensive mapping of the organization of the lymphatic endothelial network entering and exiting LNs in health and in chronic infectious diseases in a nonhuman primate model. The differences we have defined between the afferent and efferent interfaces of LNs could inform the future design of vaccines and immunotherapies.     

Renorenal reflexes: interaction between efferent and afferent renal nerve activity.

In rats, stimulation of renal mechanoreceptors by increasing ureteral pressure results in a contralateral inhibitory renorenal reflex response consisting of increases in ipsilateral afferent renal nerve activity, decreases in contralateral efferent renal nerve activity, and increases in contralateral urine flow rate and urinary sodium excretion. Mean arterial pressure is unchanged. To study possible functional central interaction among the afferent renal nerves and the aortic and carotid sinus nerves, the responses to renal mechanoreceptor stimulation were compared in sinoaortic denervated rats and sham-denervated rats before and after vagotomy. In contrast to sham-denervated rats, there was an increase in mean arterial pressure in response to renal mechanoreceptor stimulation in sinoaortic-denervated rats. However, there were no differences in the renorenal reflex responses among the groups. Thus, our data failed to support a functional central interaction among the renal, carotid sinus, and aortic afferent nerves in the renorenal reflex response to renal mechanoreceptor stimulation. Studies to examine peripheral interaction between efferent and afferent renal nerves showed that marked reduction in efferent renal nerve activity produced by spinal cord section at T6, ganglionic blockade, volume expansion, or stretch of the junction of superior vena cava and right atrium abolished the responses in afferent renal nerve activity and contralateral renal function to renal mechanoreceptor stimulation. Conversely, increases in efferent renal nerve activity caused by thermal cutaneous stimulation increased basal afferent renal nerve activity and its responses to renal mechanoreceptor stimulation. These data suggest a facilitatory role of efferent renal nerves on renal sensory receptors.     

The role of sensory neurons in cervical ripening: effects of estrogen and neuropeptides.

Central nervous system nuclei and circuits, such as the medial preoptic, ventromedial and paraventricular nuclei of the hypothalamus, play important roles in reproduction and parturition, and are influenced by estrogen. Peripheral autonomic and sensory neurons also play important roles in pregnancy and parturition. Moreover, the steroid hormone estrogen acts directly, not only on the reproductive tract organs (uterus and cervix), but also on the central and peripheral nerves by regulating expression of various neuronal genes. The peripheral primary afferent neurons innervating the uterine cervix relay mechanical and biochemical sensory information induced by local cervical events and by passage of fetuses, to the spinal cord and supraspinal centers. Consequently, the birth process in mammals is influenced by the combined action of neurons and hormones. Peripheral sensory stimuli, induced physiologically by fetal expulsion or mechanically by vaginocervical stimulation, alter behavior, as well as autonomic and neuroendocrine systems. Recent evidence indicates that primary afferent neurons innervating the cervix, in addition to their sensory effects, likely exert local "efferent" actions on the ripening cervix near term. These efferent effects may involve estrogen-regulated production of such neuropeptides as substance P and calcitonin gene-related peptide in lumbosacral dorsal root ganglia, and their release in the cervix. Collectively, these findings suggest an interrelationship among estrogen, cervix-related sensory neurons, and local cervical events near term.     

The Ulrastructure of the Gill of the Lugworm Arenicola marina (L.) (Annelida,Polychaeta)

Arenicola marina gills are hollow, branched, body outgrowths with a central coelomic cavity and afferent and efferent vessels. The gill surface area per unit body weight is about 4 cm²/g wet weight. The blood vascular system anatomy differs from the tip to the base of the gill. In the distal branches of the gill the superficial afferent and efferent vessels are joined by connecting vessels. All vessels arise as spacings between the basal laminae of the thin epidermis and of the coelomic myoepithelium. The contractile part of this epithelium mainly borders the afferent and efferent vessels, whereas pedicel-like cytoplasmic processes extend from the cell bodies and mainly line the connecting vessels. In the proximal branches of the gill the afferent and efferent vessels located in the coelomic cavity are surrounded by the coelomic myoepithelium, and a peripheral blood plexus is present below the epidermis. The gill epidermis is everywhere thin and does not exhibit the characters of a transporting epithelium. The gill coelomic myoepithelium has several functions: (i) periodic contractions of the gill, propelling blood and coelomic fluid toward the central vascular and coelomic compartments; (ii) blood ultrafilration toward the coelomic cavity; (iii) probably transport, suggested by the specialized structures of the lateral membranes of the cells.     

Suppression of antigraft immunity by preimmunization. III. Characterization of suppressor T cells involved in suppression of the efferent phase of DTH against alloantigens

Suppressor T (Ts) cells that can suppress delayed type hypersensitivity (DTH) against histocompatibility (H) antigens can be isolated from spleen and lymph nodes a few days after i.v. immunization of mice with irradiated allogeneic spleen cells. In this paper we investigated the suppression of the efferent phase of DTH to characterize the Ts cells involved, and to compare them with the afferent phase Ts cells that have been characterized in a previous paper of this series. The DTH against third party alloantigens that were not used for the i.v. suppressive immunization could be suppressed by presenting the third party alloantigens together with the original alloantigens in the challenge inoculum for eliciting the DTH reaction. Thus the ultimate suppressive effect by the Ts cells that are active during the efferent phase of DTH is nonspecific. This non-specific suppression of DTH to alloantigens has previously been found for the afferent phase Ts cells as well. For suppression of the efferent phase of DTH to alloantigens, a population of Lyt-1+2+ Ts cells appeared to be essential, just like in the suppression of the afferent phase of DTH to alloantigens. We did not find evidence for the involvement of cyclophosphamide-sensitive auxiliary Ts cells in suppression of the efferent phase of DTH. Also no evidence was found for H-2 or Igh-restricted activation and function of the Ts cells that were active during afferent and efferent phases of the DTH response to H antigens. In view of these similarities between afferent phase and efferent phase Ts cells we conclude that there are no arguments as yet to suppose that there is more than one type of T cells involved in the suppression of the afferent and efferent limb of DTH against H antigens.     

Heat attenuates sensitivity of mammalian cells to capsaicin

The transient receptor potential (TRP) channels are thermo‐sensors, and transient receptor potential vanilloid (TRPV)1 and V4 are widely expressed in primary afferent neurons and nonneuronal cells. Although heat acclimation is considered as changes of thermoregulatory responses by thermo‐effectors to heat, functional changes of TRP channels in heat acclimation has not been fully elucidated. Here, we investigated whether heat acclimation induces capsaicin tolerance. NIH3T3 cells were incubated at 39.5°C. We determined the expression level of TRPV1 and TRPV4 messenger RNA (mRNA), performed cellular staining of TRPV1 and TRPV4, and investigated actin assembly and activation of the extracellular signal‐regulated kinase (ERK). Exposure to moderate heat decreased the levels of TRPV1 but not TRPV4 mRNA. It also induced stress fiber formation and the intensity of TRPV1 seemed to be decreased by chronic heat stimuli. In addition, heat acclimation attenuated the capsaicin‐induced activation of ERK. Heat acclimation may induce capsaicin tolerance via the downregulation of TRPV1.     

The renal afferent nerves in the pathogenesis of hypertension

The renal nerves play a role in the pathogenesis of hypertension in a number of experimental models. In the deoxycorticosterone acetate - salt (DOCA-NaCl) hypertensive rat and the spontaneously hypertensive rat (SHR) of the Okamoto strain, total peripheral renal denervation delays the development and blunts the severity of hypertension and causes an increase in urinary sodium excretion, suggesting a renal efferent mechanism. Further, selective lesioning of the renal afferent nerves by dorsal rhizotomy reduces hypothalamic norepinephrine stores without altering the development of hypertension in the SHR, indicating that the renal afferent nerves do not play a major role in the development of hypertension in this genetic model. In contrast, the renal afferent nerves appear to be important in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats (1K, 1C and 2K, 1C, respectively) and in dogs with chronic coarctation hypertension. Total peripheral renal denervation attenuates the severity of hypertension in these models, mainly by interrupting renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure. Peripheral renal denervation has a peripheral sympatholytic effect and alters the level of activation of central noradrenergic pathways but does not alter sodium or water intake or excretion, plasma renin activity or creatinine clearance, suggesting that efferent renal nerve function does not play an important role in the maintenance of this form of hypertension. Selective lesioning of the renal afferent nerves attenuates the development of hypertension, thus giving direct evidence that the renal afferent nerves participate in the pathogenesis of renovascular hypertension.     

Two modes of pseudorabies virus neuroinvasion and lethality in mice

We describe two distinct modes of neuroinvasion and lethality after murine flank inoculation with virulent and attenuated strains of pseudorabies virus (PRV). Mice infected with virulent (e.g., PRV-Becker, PRV-Kaplan, or PRV-NIA3) strains self-mutilate their flank skin in response to virally induced pruritus, die rapidly with no identifiable symptoms of central nervous system (CNS) infection such as behavioral abnormalities, and have little infectious virus or viral antigen in the brain. In distinct contrast, animals infected with an attenuated PRV vaccine strain (PRV-Bartha) survive approximately three times longer than wild-type PRV-infected animals, exhibit severe CNS abnormalities, and have an abundance of infectious virus in the brain at the time of death. Interestingly, these animals have no skin lesions and do not appear pruritic at any time during infection. The severe pruritus and relatively earlier time until death induced by wild-type PRV infection may reflect the peripheral nervous system (PNS) and immune responses to infection rather than a fatal, virally induced CNS pathology. Based on previously characterized afferent (sensory) and efferent (motor) neuronal pathways that innervate the skin, we deduced that wild-type virulent strains transit through the PNS via both afferent and efferent routes, whereas PRV-Bartha travels by only efferent routes in the PNS en route to the brain.     

Neural regulation of the cardiovascular system during exercise

Neural components important in control of the cardiovascular system during exercise can be divided into central nervous system (CNS) components and peripheral components. CNS components would include the cerebral cortex, cerebellum, medullary region of the brain stem, and the spinal cord. Peripheral components would include the efferent limbs of the autonomic nervous system and afferent fibers carrying information to the CNS. The neural pathways involved in the control of cardiovascular system during exercise and the relationship between the various neural components have been actively pursued in the last few years. Several new studies suggest that information arising from the active muscles and the cardiovascular system itself may be important in the control of the cardiovascular system during exercise. The cerebellum may play a modulating role in the cardiovascular response. The information from the peripheral afferent fibers, the cerebellum, and the cerebral cortex is integrated in the brain to result in overall neural control. Exercise training probably modifies the central integration of information and modifies the cardiovascular response to exercise and other stresses.     

Neuronal control of the kidney: contribution to hypertension.

The renal nerves contribute to hypertension in experimental models of the disease, and appear to play a role in human hypertension. Several lines of evidence indicate that both in spontaneously hypertensive rats and in deoxycorticosterone acetate--NaCl rats, the full development of hypertension is dependent on renal efferent nerves and their induction of excess sodium retention. Renal sensory (afferent nerve) feedback to the central nervous system does not contribute to either of these forms of hypertension. In contrast, renovascular hypertension in rats and aortic coarctation hypertension in dogs are mediated, at least in part, by overactivity of renal afferent nerves and a resultant increase in systemic sympathetic nervous system activity. These forms of hypertension are not associated with sodium retention, and selective sensory denervation of renal afferent nerves by dorsal rhizotomy and total renal denervation result in similar reductions in hypertension. Surprisingly, the renal nerves do not contribute to dietary NaCl exacerbated hypertension in the spontaneously hypertensive rat, dietary NaCl-induced hypertension in the Dahl NaCl-sensitive rat, or the chronic hypertensive and nephrotoxic effects of cyclosporine A therapy in the rat, despite the finding that in all three forms of hypertension, overactivity of the sympathetic nervous system is prominent. Clinical studies indicate that the renal afferent and efferent nerves contribute to hypertension of different etiologies. Together these data point to the complex role that the renal nerves likely play in human essential hypertension.     

Reflex regulation of airway smooth muscle tone.

Autonomic nerves in most mammalian species mediate both contractions and relaxations of airway smooth muscle. Cholinergic-parasympathetic nerves mediate contractions, whereas adrenergic-sympathetic and/or noncholinergic parasympathetic nerves mediate relaxations. Sympathetic-adrenergic innervation of human airway smooth muscle is sparse or nonexistent based on histological analyses and plays little or no role in regulating airway caliber. Rather, in humans and in many other species, postganglionic noncholinergic parasympathetic nerves provide the only relaxant innervation of airway smooth muscle. These noncholinergic nerves are anatomically and physiologically distinct from the postganglionic cholinergic parasympathetic nerves and differentially regulated by reflexes. Although bronchopulmonary vagal afferent nerves provide the primary afferent input regulating airway autonomic nerve activity, extrapulmonary afferent nerves, both vagal and nonvagal, can also reflexively regulate autonomic tone in airway smooth muscle. Reflexes result in either an enhanced activity in one or more of the autonomic efferent pathways, or a withdrawal of baseline cholinergic tone. These parallel excitatory and inhibitory afferent and efferent pathways add complexity to autonomic control of airway caliber. Dysfunction or dysregulation of these afferent and efferent nerves likely contributes to the pathogenesis of obstructive airways diseases and may account for the pulmonary symptoms associated with extrapulmonary disorders, including gastroesophageal reflux disease, cardiovascular disease, and rhinosinusitis.     

Efferent fibers innervate gustatory and mechanosensitive afferent fibers in frog fungiform papillae

A possibility of efferent innervation of gustatory and mechanosensitive afferent fiber endings was studied in frog fungiform papillae with a suction electrode. The amplitude of antidromic impulses in a papillary afferent fiber induced by antidromically stimulating an afferent fiber of glossopharyngeal nerve (GPN) with low voltage pulses was inhibited for 40 s after the parasympathetic efferent fibers of GPN were stimulated orthodromically with high voltage pulses at 30 Hz for 10 s. This implies that electrical positivity of the outer surface of papillary afferent membrane was reduced by the efferent fiber-induced excitatory postsynaptic potential. The inhibition of afferent responses in the papillae was blocked by substance P receptor blocker, L-703,606, indicating that substance P is probably released from the efferent fiber terminals. Slow negative synaptic potential, which corresponded to a slow depolarizing synaptic potential, was extracellularly induced in papillary afferent terminals for 45 s by stimulating the parasympathetic efferent fibers of GPN with high voltage pulses at 30 Hz for 10 s. This synaptic potential was also blocked by L-703,606. These data indicate that papillary afferent fiber endings are innervated by parasympathetic efferent fibers.     

Infection of mice with Newcastle disease virus inhibits the T suppressor afferent cell circuit which regulates contact sensitivity to picryl chloride

The interaction between Newcastle disease virus (NDV) and the suppressor cell circuit which regulates the induction phase of contact sensitivity reaction to picryl chloride (Pcl) was investigated. NDV infection impairs the activity of the T suppressor afferent cells (Ts-aff) which inhibit DNA synthesis in the draining lymph nodes of mice specifically sensitized with Pcl and the development of contact sensitivity. The inhibitory effect of NDV was evident when the virus was administered up to 2 days before or at the same time as the injection of picrylsulfonic acid; this effect required infectious virus, as NDV inactivated by ultraviolet irradiation failed to inhibit Ts-aff activity. Taken together with the previous finding that the T suppressor efferent cell is unaffected by NDV, the present results support the view that contact sensitivity reaction to picryl chloride is regulated by two distinct T-suppressor-cell circuits.     

Simulation of human arm movements controlled by peripheral feedback

A model of the human arm, suitable for simulation purposes, is presented in order to investigate whether it is possible that peripheral feedback can play an important role during fast arm movements. In spite of factors such as the inertia of the system, the slow regulation of muscle tension, and efferent and afferent conduction delays between the muscles and the motorneuronal pools, it appears from the simulations that peripheral feedback of proprioceptive information could indeed be effective even during fast movements.     

Analysis of afferent,central, and efferent components of the baroreceptor reflex in mice

Studies of genetically modified mice provide a powerful approach to investigate consequences of altered gene expression in physiological and pathological states. The goal of the present study was to characterize afferent, central, and efferent components of the baroreceptor reflex in anesthetized Webster 4 mice. Baroreflex and baroreceptor afferent functions were characterized by measuring changes in renal sympathetic nerve activity (RSNA) and aortic depressor nerve activity (ADNA) in response to nitroprusside- and phenylephrine-induced changes in arterial pressure. The data were fit to a sigmoidal logistic function curve. Baroreflex diastolic pressure threshold (P(th)), the pressure at 50% inhibition of RSNA (P(mid)), and baroreflex gain (maximum slope) averaged 74 +/- 5 mmHg, 101 +/- 3 mmHg, and 2.30 +/- 0.54%/mmHg, respectively (n = 6). The P(th), P(mid), and gain for the diastolic pressure-ADNA relation (baroreceptor afferents) were similar to that observed for the overall reflex averaging 79 +/- 9 mmHg, 101 +/- 4 mmHg, and 2.92 +/- 0.53%/mmHg, respectively (n = 5). The central nervous system mediation of the baroreflex and the chronotropic responsiveness of the heart to vagal efferent activity were independently assessed by recording responses to electrical stimulation of the left ADN and the peripheral end of the right vagus nerve, respectively. Both ADN and vagal efferent stimulation induced frequency-dependent decreases in heart rate and arterial pressure. The heart rate response to ADN stimulation was nearly abolished in mice anesthetized with pentobarbital sodium (n = 4) compared with mice anesthetized with ketamine-acepromazine (n = 4), whereas the response to vagal efferent stimulation was equivalent under both types of anesthesia. Application of these techniques to studies of genetically manipulated mice can be used to identify molecular mechanisms of baroreflex function and to localize altered function to afferent, central, or efferent sites.