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Biomedical subjects

P Gonnella

Publications and source records attributed to P Gonnella.

7 recordsLinked to original sources
PubMed1998

Mechanisms of recovery from experimental autoimmune encephalomyelitis: T cell deletion and immune deviation in myelin basic protein T cell receptor transgenic mice.

Experimental autoimmune encephalomyelitis (EAE) is a Th1-type cell-mediated autoimmune disease directed against central nervous system (CNS) myelin antigens such as myelin basic protein (MBP). EaE is usually characterized by spontaneous remission of clinical disease and immune pathology despite the persistence of self myelin antigens in the central nervous system. Following induction of an acute episode of EAE, spontaneous remission also occurs in MBP T cell receptor (TCR) transgenic mice even through most T cells express a TCT specific for MBP. To investigate the mechanisms of recovery associated with EAE, we examined the behavior of MBP-specific T cells in the MBP TCR transgenic mouse model during disease progression and recovery. We found that recovery from EAE was associated with three major immunologic changes: (1) deletion of encephalitogenic T cells in the brain; (2) deviation of MBP-specific transgenic (Tg+) T cells both in the periphery and in the central nervous system from INF- gamma secretin Th1 type cells to cells that secrete IL-4, IL-10, and TGF- beta ; and (3) deletion of Tg+ T cells in the thymus through apoptosis. Thus spontaneous recovery from a classic Th1 type organ specific autoimmune disease is associated with two mechanisms of immune tolerance, deletion of autoreactive cells and immune deviation of autoreactive cells to a non-pathogenic phenotype.

Animals↗
PubMed1995

Peripheral deletion of antigen-reactive T cells in oral tolerance.

Oral administration of antigen is used to induce antigen-specific peripheral immune tolerance. As well as preventing systemic immune responses to ingested proteins, oral tolerance to autoantigens has also been used to suppress autoimmune diseases in animals and humans. Both active suppression and clonal anergy are suggested to be mechanisms of oral tolerance, depending on the dose of antigen fed. Here we report that oral antigen can delete antigen-reactive T cells in Peyer's patches, in mice transgenic for the ovalbumin-specific T-cell receptor genes. The deletion was mediated by apoptosis, and was dependent on dosage and frequency of feeding. At lower doses deletion was not observed; instead there was induction of antigen-specific cells that produced transforming growth factor (TGF)-beta and interleukin (IL)-4 and IL-10 cytokines. At higher doses, both Th1 and Th2 cells were deleted following their initial activation, whereas cells which secrete TGF-beta were resistant to deletion. These findings demonstrate that orally administered antigen can induce tolerance not only by active suppression and clonal anergy but by extrathymic deletion of antigen-reactive Th1 and Th2 cells.

Administration, Oral↗
PubMed1990

Diffuse necrotizing retinochoroiditis in a child with AIDS and toxoplasmic encephalitis.

We examined a child with a human immunodeficiency virus (HIV) infection who at 15 months of age developed acute encephalitis, followed 1 week later by a diffuse, uniocular retinochoroiditis. The clinical picture in the right eye was characterized by the occurrence of some intraretinal hemorrhages; punctate, yellow-white, outer retinal lesions temporal to the macula; and a quadrantal, white area of necrotic retina located superotemporally. - The vitreous was remarkably clear, and the left eye was normal. Fluorescein angiography revealed small spots of late hyperfluorescence, vasculitis in the posterior pole, and a persistently hypofluorescent quadrantal superotemporal area. Toxoplasma IgM antibodies that were absent 1 week after birth became detectable in the serum and the cerebrospinal fluid. Serological testing for cytomegalovirus was negative. Neurological signs improved on a specific therapy (pyrimethamine and sulfamethopirazine), but the patient died 2 months later of disseminated cytomegalovirus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Inhibitory effect of calcitonin gene-related peptide and calcitonin on opossum esophageal smooth muscle.

Calcitonin gene-related peptide (CGRP) is widely distributed in the gastrointestinal nerves, including those of the esophagus. The present investigation was undertaken to examine the effect and the mechanism of action of CGRP on the lower esophageal sphincter and esophageal contractions. This peptide caused dose-dependent relaxation of the lower esophageal sphincter. The D50 for inhibitory effect of intraarterial CGRP on the sphincter was 5.0 X 10(-13) mol/kg. Calcitonin gene-related peptide is 3000 times more potent than calcitonin. The effect of CGRP on the lower esophageal sphincter was partially antagonized by tetrodotoxin or black widow spider venom. The inhibitory effect of CGRP on the sphincter appears to be exerted at two levels: (a) at the sphincteric smooth muscle, and (b) at the noncholinergic, nonadrenergic inhibitory neurons. Calcitonin gene-related peptide also exerts a potent inhibitory effect on the peristaltic contraction of the esophageal body in response to swallowing and vagal efferent stimulation. Using immunohistochemical studies we also showed the presence of CGRP-immunoreactive neurons within the myenteric ganglia of the esophagus. These studies suggest that CGRP may play an important role as an inhibitory neurotransmitter in the esophagus.

Animals↗
PubMed1986

Uptake and transepithelial transport of nerve growth factor in suckling rat ileum.

Nerve growth factor (NGF) is necessary for the development of sympathetic and some sensory neurons. Milk may be a source of NGF for suckling young, but sites of intestinal absorption of the protein have not been identified. To determine whether NGF is transported across the absorptive epithelium of suckling rat ileum, we assessed binding, uptake, and transport of 125I-NGF by light microscopy and EM autoradiography. Blood and tissue extracts were analyzed by biochemical and immunological methods to determine whether NGF was taken up structurally intact. NGF binding sites were identified on microvilli and apical invaginations of ileal absorptive cells in vitro. Injected into ileal loops in vivo, NGF radioactivity retained by fixation was evident after 20 min in apical regions of absorptive cells, in endocytic tubules (which mediate the uptake of membrane-bound ligands), in vesicles (which mediate nonspecific endocytosis), and in the supranuclear lysosomal vacuole. At 1 and 2 h, radiolabel in these compartments increased and silver grains were evident at the basal cell surface, and in cells, matrix, and vessels of the lamina propria. In blood and liver, radiolabeled molecules that were immunologically and electrophoretically indistinguishable from NGF and that co-eluted with NGF on gel filtration columns were detected, confirming that some NGF was transported across the epithelium structurally intact. Thus, absorptive cells of suckling rat ileum can take up NGF by both receptor-mediated and nonspecific endocytosis, and direct NGF either to the lysosome for degradation, or into a transepithelial transport pathway.

Animals↗