When engineered to produce latent TGF-beta1, antigen specific T cells down regulate Th1 cell-mediated autoimmune and Th2 cell-mediated allergic inflammatory processes.

To determine whether T cells which produce large amounts of latent TGF-beta1 are capable of down-regulating autoimmune and allergic disease, myelin basic protein (MBP)-specific and ovalbumin (OVA)-specific BALB/c cloned Th1 cells were transduced with cDNA for murine TGF-beta1 by coculture with fibroblasts producing a genetically engineered retrovirus. The transduced MBP-specific Th1 cells were found to lose the capacity to provoke EAE in BALB/c mice, and to gain instead the ability to protect against EAE in (SJLxBALB/c) F1 mice immunized with proteolipid protein (PLP). This protective effect was not obtained with OVA-specific TGF-beta1 transduced Th1 cells.

Gene therapy in allergic encephalomyelitis using myelin basic protein-specific T cells engineered to express latent transforming growth factor-beta1.

A myelin basic protein (MBP)-specific BALB/c T helper 1 (Th1) clone was transduced with cDNA for murine latent transforming growth factor-beta1 (TGF-beta1) by coculture with fibroblasts producing a genetically engineered retrovirus. When SJL x BALB/c F1 mice, immunized 12-15 days earlier with proteolipid protein in complete Freund's adjuvant, were injected with 3 x 10(6) cells from MBP-activated untransduced cloned Th1 cells, the severity of experimental allergic encephalomyelitis (EAE) was slightly increased. In contrast, MBP-activated (but not resting) latent TGF-beta1-transduced T cells significantly delayed and ameliorated EAE development.

Staphylococcal enterotoxin B and tumor-necrosis factor-alpha-induced relapses of experimental allergic encephalomyelitis: protection by transforming growth factor-beta and interleukin-10.

A study was made of the ability of the superantigen staphylococcal enterotoxin B (SEB) to induce relapses of experimental allergic encephalomyelitis (EAE) in SJL mice that had partially or completely recovered from acute EAE. We find that a single injection of 0.05 mg SEB i.

Tolerogenic forms of auto-antigens and cytokines in the induction of resistance to experimental allergic encephalomyelitis.

Resistance to experimental allergic encephalomyelitis (EAE) induction by homogenized myelin (MSCH) in complete Freund's adjuvant (CFA) and pertussigen (P) in SJL mice was seen 1 week after intravenous injection of PLP 139-151 coupled to spleen cells (PLP-ECDI-SP). Although this resistance could be transferred by spleen cells enriched for CD8+ T cells and thus had a component of immunoregulatory T cells, it was primarily due to anergy, as it was reversible by four daily injections of interleukin (II)-2 starting 3 days after the PLP-ECDI-SP. Earlier treatment with IL-2 did not reverse the tolerance.

Nerve growth factor production by lymphocytes.

Nerve growth factor (NGF) is a neurotrophic protein essential for the maintenance and growth of peripheral sympathetic neurons and basal forebrain cholinergic neurons. Recently, NGF has also been shown to have effects on cells of the immune system. In a search for extra neural sources of NGF, we detected NGF-specific mRNA in mouse T lymphocytes of both the CD4+ and CD8+ phenotypes with the use of an RNase protection assay, PCR, and DNA sequence analysis.

Brain edema resolution by CSF pathways and brain vasculature in cats.

Brain edema is a major contributor to the brain swelling process and raised intracranial pressure, yet the specific pathways involved in clearance of brain edema (fluid and proteins) and their relative contribution to the resolution process remain unknown. The objective of this study was to document the temporal course of edema resolution from brain to cerebrospinal fluid (CSF) and by the brain vasculature. Radioiodinated (125I) cat serum albumin (RICSA) was infused continuously into the white matter of anesthetized adult cats for 8 h, and ventriculocisternal perfusion was used to monitor the RICSA activity in CSF at 15-min intervals and to compare with the blood taken at 15-min intervals.

Antagonistic effects of endogenous and exogenous TGF-beta and TNF on auto-immune diseases in mice.

Injection of transforming growth factor beta 1 (TGF-beta 1) for five days during the late phase of the immunization process leading either to collagen type II induced arthritis (CIA) or to experimental allergic encephalomyelitis (EAE) protects against the development of these auto-immune diseases. Tumor necrosis factor alpha (TNF-alpha) injected during this same interval aggrevates CIA. In addition, anti-TGF-beta exacerbates and anti-TNF protects against CIA, acute and relapsing EAE, suggesting an important regulatory role for the endogenous production of the two cytokines on the severity of these diseases.

Studies on the mechanisms by which transforming growth factor-beta (TGF-beta) protects against allergic encephalomyelitis. Antagonism between TGF-beta and tumor necrosis factor.

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease in which peripheral lymphoid cells are activated by immunization with myelin proteins and become effector cells that traverse the central nervous system (CNS) capillaries and initiate inflammatory demyelinating lesions. The administration of transforming growth factor-beta (TGF-beta) has been shown previously to decrease the incidence and severity of EAE. In our studies we have determined: 1) the effects of TGF-beta injected at different intervals after the EAE-inducing immunization; 2) the effect of TGF-beta on the development of sensitized T cells, as assayed by the proliferative responses of T cells from lymph nodes and peripheral blood; 3) the extent of lymphoid cell infiltration in CNS of TGF-beta-treated and control mice; and 4) the role of endogenous TGF-beta and TNF in determining the severity of both acute and relapsing EAE.

Isolation and amino terminal sequence of beta-trace, a novel protein from human cerebrospinal fluid.

beta-Trace, a 23.5 kDa glycoprotein of unknown biological functions, is present in all body fluids tested. It is found in higher concentration in human seminal fluid and cerebrospinal fluid (CSF) than in serum.

Protective effect of transforming growth factor beta 1 on experimental autoimmune diseases in mice.

Interleukin 1 (IL-1) and tumor necrosis factor alpha are thought to contribute to the inflammatory response associated with autoimmune diseases. Transforming growth factor beta 1 (TGF-beta 1) counteracts many effects of these cytokines and has various immunosuppressive properties. In the present study, it is shown that microgram amounts of TGF-beta 1, injected daily for 1-2 weeks, protect against collagen-induced arthritis (CIA) and relapsing experimental allergic encephalomyelitis (REAE), the animal models for rheumatoid arthritis and multiple sclerosis, respectively.

Immune response in draining lymph nodes and spleen after intraventricular injection of antigen.

Both Fischer 344 and Sprague Dawley rats showed significant numbers of antibody forming cells (PFC) in deep cervical lymph nodes after intraventricular injection of antigens, including trinitrophenylated (TNP)-hemocyanin, TNP-B. abortus and sheep erythrocytes. This indicated that particular as well as soluble antigens drained to these lymph nodes from the spinal fluid.

Primary and secondary wattle swelling response to phytohemagglutinin as a measure of immunocompetence in chickens.

Wattle responses of 2-to-8-week-old chickens to phytohemagglutinins PHA-P and PHA-M were studied. Dilutions of PHA-M that did not induce wattle swelling after one injection did cause readily detectable swelling when injected a second time 1 week later. These responses were absent in birds subjected to thymectomy and gamma-irradiation at hatching and in birds treated with cyclosporin A during the week of sensitization, indicating that these responses are T-cell-dependent.

Cerebrospinal fluid glucose: turnover and metabolism.

The turnover of cerebrospinal fluid (CSF) glucose was studied in cats during steady-state perfusion. In all experiments, the perfusion fluid contained either tracer [14C]glucose alone or tracer glucose along with 4.45 mM unlabeled glucose.

Immunity to transplantable nitrosourea-induced neurogenic tumors. III. Systemic adoptive transfer of immunity.

The effect of intravenously injected tumor immune spleen cells on growth of 3 X 10(5) gliosarcoma T9 cells injected intradermally (ID) or intracerebrally (IC) into sublethally irradiated CDF rats was evaluated. Spleen cells from donor rats with sufficient immunity to reject 5 X 10(5) T9 cells inhibited the growth of T9 cells mixed with spleen cells in a ratio of 1:25 and injected ID, but could not act after intravenous transfer. However, donor rats which had rejected increasing T9 challenge doses up to 1 X 10(7) cells produced immune spleen cells which, upon IV transfer, could inhibit growth of ID T9 challenge but not of EB-679, an unrelated glioma, in recipient rats.

Cerebrospinal fluid glucose and leukocyte responses in experimental meningitis.

The fall in cerebrospinal fluid (CSF) glucose and CSF leukocyte response was studied in cats with experimental meningitis. Klebsiella pneumoniae or Streptococcus pneumoniae were injected intracisternally, and the latter organisms were incubated with CSF in vitro. When 10(6)-10(9)K.

Net transport of glucose from blood to cerebrospinal fluid in the cat.

The net transport of glucose from blood to the cerebrospinal fluid compartment of cats was measured by ventriculocisternal perfusion to determine over a large range of serum glucose concentrations the influence of serum glucose levels and their changes on the net transport rate. Changes in serum glucose levels were followed within minutes by corresponding changes in cerebroventricular effluent fluid glucose concentration. At mean values of serum glucose concentration of 6.

Enkephalin-induced changes in ventilation and ventilatory pattern in adult dogs.

We studied the changes in ventilation induced by intracisternal administration of enkephalins in four unanesthetized adult dogs. Instantaneous minute ventilation (VT/TT) decreased markedly after D-Ala-Met-enkephalinamide (DAME). Mean VT/TT decreased maximally by 20-50 min after DAME and lasted an additional 15-60 min; by 2 h, VT/TT had returned to base line.

Spinal fluid formation and glucose influx in normal and experimental hydrocephalic rats.

Cerebrospinal fluid (CSF) turnover and glucose influx were measured in normal and kaolin-induced hydrocephalic rats. The CSF formation rate of normal rats was 2.8 microliter/min and after intracisternal kaolin it was reduced to 1.

Immunity to transplantable nitrosourea-induced neurogenic tumors. II. Immunoprophylaxis of tumors of the brain.

An effective method was sought to immunize rats against the growth of intracerebrally (IC) injected T9 tumor, a gliosarcoma cell line. Rats which were immunized with either 10(6) T9 cells mixed with 0.14 mg C.

Pressure-absorption responses to the infusion of fluid into the spinal cord central canal of kaolin-hydrocephalic cats.

The resistance to cerebrospinal fluid (CSF) absorption through the alternative CSF absorption pathway in kaolin-induced hydrocephalic cats was measured by the constant infusion-manometric test. The cerebral ventricles were bypassed, and artificial CSF was infused directly into the central canal of the spinal cord. The infusion rates were increased stepwise from 0.

Derivation of transplantable 7,12-dimethylbenz[a]anthracene-induced chicken fibrosarcoma lines: differences in metastasizing properties and organ specificity.

Several transplantable 7,12-dimethylbenz[a]anthracene-induced SC chicken fibrosarcoma (CHCT-NYU) lines were studied for their ability to grow in internal organs after iv injection (artificial metastases) into 1- to 3-week-old chickens. Some tumor lines were recently derived, whereas others were studied after many serial subcutaneous transplantations. STriking similarities as well as differences were found between tumor lines' ability to grow in various organs.