Perivascular Mononuclear Cell Infiltrates Research Articles

The evaluation of aluminum oxide crystal microdermabrasion for photodamage.

Aluminum oxide crystal microdermabrasion has recently become popular for facial rejuvenation. Although it is a widely used technique with perceptible benefits, the clinical efficacy on photodamaged skin has yet to be established. To measure and quantify the effect of microdermabrasion on photodamaged skin. Ten subjects underwent one treatment a week for five to six treatments. Skin surface roughness, topography, elasticity, stiffness, compliance, temperature, sebum content, and histology were analyzed. Subjectively, seven patients noticed a mild improvement. Physician analysis of clinical photography indicated mild improvement in the majority of patients. Objectively, immediately following treatment skin temperature increased, sebum content decreased, and a temporary increase in skin roughness and mild flattening of some wrinkles occurred. Dynamic skin analysis demonstrated a perceptible decrease in skin stiffness and an increase in skin compliance. Histology showed slight orthokeratosis and flattening of rete ridges and a perivascular mononuclear cell infiltrate, edema, and vascular ectasia in the upper reticular dermis 1 week after completion of the series of treatments. Immediately following the procedure, changes occurring in skin characteristics can be measured that are consistent with mild abrasion and increased blood flow. Objective biomechanical analysis demonstrated a statistically significant decrease in skin stiffness and an increase in skin compliance consistent with persistent edema. Subjectively, patients and physicians report a mild improvement in the majority of subjects. Histology showed dramatic vascular changes in the reticular dermis below the level of direct abrasion. The effect of negative pressure may result in these vascular changes.

Chronic inflammation and protection from acute hepatitis in transgenic mice expressing TNF in endothelial cells.

Endothelial activation is an important feature of many inflammatory diseases and has been implicated as the cause of vascular complications in disorders such as diabetes, atherosclerosis, and transplant rejection. One of the most potent activators of the endothelium is TNF, which can also be expressed by endothelial cells, causing a permanent, autocrine stimulatory signal. To establish a model of continuous endothelial activation and to elucidate the role of endothelial derived TNF in vivo, we generated transgenic mice expressing a noncleavable transmembrane form of TNF under the control of the endothelial-specific tie2 promoter. Adult tie2-transmembrane TNF-transgenic mice developed chronic inflammatory pathology in kidney and liver, characterized by perivascular infiltration of mononuclear cells into these organs. Along with the infiltrate, an up-regulation of the adhesion molecules ICAM-1 and VCAM-1, but not E-selectin, in the endothelium was observed. Despite predisposition to chronic inflammation these mice were protected from immune-mediated liver injury in a model of Con A-induced acute hepatitis. Although the blood levels of soluble TNF and IFN-gamma were increased in transgenic animals after challenge with Con A, no damage of hepatocytes could be detected, as assessed by the lack of increase in plasma transaminase activities and the absence of TUNEL staining in the liver. We conclude that expression of transmembrane TNF in the endothelium causes continuous endothelial activation, leading to both proinflammatory and protective events.

Prevention of autoantibody formation and prolonged survival in New Zealand Black/New Zealand White F1 mice with an ancient Chinese herb, Ganoderma tsugae

For centuries, Chinese medicine has regarded Ganoderma, a fungus (Myceteae, Amastigomycota, Busidomycetes, Aphyllophorales, Polyporaceae, Ganoderma) also known as 'Ling Zhi' in Mandarin, as a premium remedy for many diseases. Until now, no convincing data regarding its therapeutic effects in vivo on autoimmune diseases have been demonstrated. In this study, a controlled protocol was conducted in which New Zealand Black/White F1 mice were fed standard chow with prednisolone (0.5 mg/kg/day) or Ganoderma tsugae extract, commencing at 2 months of age. It was found that the F1 mice responded well to Ling Zhi extract. Ling Zhi improved the survival rate of lupus mice, decreased the amount of proteinuria, decreased serum levels of anti-dsDNA autoantibody, and showed evidence of decreased perivascular and parenchyma mononuclear cell infiltration in vital organs.

Equine herpesvirus 9 induced lethal encephalomyelitis in experimentally infected goats.

The pathogenicity of a new neurotropic equine herpesvirus 9 (EHV-9) formerly designated gazelle herpesvirus 1 was evaluated using the goat as a representative of domesticated ruminants. Two goats inoculated intranasally with EHV-9 showed salivation, teeth grinding and other neurological disorders on day 8 post inoculation. One goat died 30 min after the onset of clinical signs and the other was sacrificed 3 h after the sudden onset of teeth grinding and foamy salivation. EHV-9 was recovered from peripheral white blood cells, the olfactory bulbs and brain, nasal swabs, concha, and lungs. Neuropathological lesions were located in the olfactory bulbs, cerebrum, midbrain and medulla oblongata with degeneration and necrosis of neurons, rarefaction, perivascular infiltration of mononuclear cells, and nodal glial reaction. EHV-9 antigen was detected in neurons in the lesions. These findings indicated that EHV-9 is highly pathogenic with high neurotropism for goats.

Persistent rat virus infection in smooth muscle of euthymic and athymic rats.

Rat virus (RV) infection can cause disease or disrupt responses that rely on cell proliferation. Therefore, persistent infection has the potential to amplify RV interference with research. As a step toward determining underlying mechanisms of persistence, we compared acute and persistent RV infections in infant euthymic and athymic rats inoculated oronasally with the University of Massachusetts strain of RV. Rats were assessed by virus isolation, in situ hybridization, and serology. Selected tissues also were analyzed by Southern blotting or immunohistochemistry. Virus was widely disseminated during acute infection in rats of both phenotypes, whereas vascular smooth muscle cells (SMC) were the primary targets during persistent infection. The prevalence of virus-positive cells remained moderate to high in athymic rats through 8 weeks but decreased in euthymic rats by 2 weeks, coincident with seroconversion and perivascular infiltration of mononuclear cells. Virus-positive pneumocytes and renal tubular epithelial cells also were detected through 8 weeks, implying that kidney and lung excrete virus during persistent infection. Viral mRNA was detected in SMC of both phenotypes through 8 weeks, indicating that persistent infection includes virus replication. However, only half of the SMC containing viral mRNA at 4 weeks stained for proliferating cell nuclear antigen, a protein expressed in cycling cells. The results demonstrate that vasculotropism is a significant feature of persistent infection, that virus replication continues during persistent infection, and that host immunity reduces, but does not eliminate, infection.

Morphologic and immunohistochemical features of experimentally induced allergic contact dermatitis in Göttingen minipigs.

Many preclinical studies in investigative dermatology are performed preferably in pigs because pig skin is more similar to human skin than is rodent skin. A frequently used model is allergic contact dermatitis (ACD); however, this T-cell-mediated skin condition so far is not well characterized in pigs. The present study is aimed at the evaluation of morphologic and immunohistochemical features of experimentally induced acute ACD in Göttingen minipigs using 2,4-dinitrofluorobenzene (DNFB) as a hapten. Eight minipigs were sensitized with 10% DNFB and challenged 2 weeks later at different sites with 1% DNFB. In addition to clinical examinations, cutaneous blood flow was quantified by laser Doppler velocimetry (Periflux PF3). These examinations were performed before challenge and 8, 24, 48, and 72 hours after challenge. Skin biopsies were taken at the same time points, fixed, sectioned, and stained with Giemsa for histologic evaluation, or with mouse anti-swine monoclonal antibodies (CD1, CD2, CD4, CD5, CD8, CD25, CD45, MHCII) and with one mouse anti-human monoclonal antibody (CD62E) cross-reacting with swine for immunohistochemical evaluation. Positively stained cells were counted per square millimeter of epidermis and dermis by using a video image analyzing system (Videoplan Kontron). Erythema and cutaneous blood flow peaked at 24 hours. The major epidermal changes most pronounced at 48 hours were acanthosis, spongiosis, intracellular edema, exocytosis, and abscesses mainly containing neutrophils and mononuclear cells (MNC). Perivascular infiltrates of MNC as well as neutrophils and eosinophils were the most significant dermal changes, with peak levels at 24-48 hours. In biopsies taken before challenge, CD1+ dendritic cells were found in similar numbers and locations as MHCII+ cells in the epidermis. In the epidermis the maximum CD1+ cell decrease occurred at 24 hours whereas in the dermis the maximum increase in CD1+ stained cells was seen at 72 hours. The dermal infiltrate (CD2+, CD5+, CD25+, and CD45+) was most dense at 48 hours. Between 8 and 48 hours more CD4+ were present than CD8+, cells, whereas at 72 hours CD4+ and CD8+ cells were similar in numbers. These findings closely resemble changes in human ACD. Therefore, DNFB-induced ACD in Göttingen minipigs is considered to be an appropriate animal model to study immunopathologic mechanisms and pharmacologic intervention.

Induction of experimental allergic encephalomyelitis in the NIH minipig

Experimental allergic encephalomyelitis (EAE) was induced in the NIH minipig to create a large animal model of multiple sclerosis with a well-characterized immune system. Sixteen NIH minipigs were inoculated with minipig spinal cord homogenate (SCH). The clinical course was primarily monophasic, but re-induction was possible. CNS and blood lymphocytes specifically proliferated to SCH. Flow cytometry of CNS-isolated cells and SCH-stimulated PBMC revealed a shift to CD4 + CD8 + cells. Pathology demonstrated demyelination in the CNS white matter with perivascular mononuclear cell infiltrates of CD3 +CD4 +CD45 + lymphocytes with a subset CD8 +. Pathology and in vitro SCH responses implicate a central role of CD4 + lymphocytes in swine EAE.

Sensitization to inhaled antigen by intratracheal instillation of dendritic cells.

Airway dendritic cells (DCs) capture and present inhaled antigen. It is not known whether antigen presentation by DCs in the airways is sufficient to induce sensitization to inhaled antigen in vivo. Rats were immunized by intratracheal instillation of ovalbumin (OVA) -pulsed bone marrow-derived DCs or macrophages and exposed 10 days later to a 30-min aerosol of OVA on 3 consecutive days. Total and differential cell counts and flow cytometry on bronchoalveolar lavage (BAL) fluid, airway histology and serum OVA-immunoglobulin (Ig) E levels were analysed 24 h after the last exposure. As few as 2 x 104 OVA-DC induced sensitization to inhaled OVA. The secondary response to OVA-aerosol consisted of an antigen-specific increase in the number of bronchoalveolar mononuclear cells, activated CD4-positive alphabeta-TCR T lymphocytes, neutrophils and few eosinophils. Peribronchial and perivascular mononuclear cell infiltrates were seen on histological analysis. There was no production of systemic OVA-IgE. Bone marrow-derived macrophages did not induce sensitization. Delivering antigen to the respiratory tract via professional antigen-presenting DCs sensitizes for a secondary response to inhaled antigen leading to airway inflammation. This model will prove very useful for studying the early events of sensitization to inhaled antigen using the respiratory route.

Pathogenicity of a new neurotropic equine herpesvirus 9 (gazelle herpesvirus 1) in horses.

Pathogenicity of equine herpesvirus 9 (EHV-9), a new type of equine herpesvirus isolated from Gazella thomsoni, in horses was investigated by intranasal inoculation of EHV-9 (10(7) pfu) to two conventionally reared 8-months old half-bred weanling horses. Fever higher than 39 degrees C was recorded. Virus was recovered from nasal swabs and peripheral blood mononuclear cells. Both horses developed neutralizing antibody to EHV-9. Perivascular infiltration of mononuclear cells and glial reaction were found in the olfactory and limbic systems. The results suggested that EHV-9 has a pathogenicity in horses.

Epidermal cytokines in experimental contact dermatitis

Topical exposure to a variety of xenobiotics may result in irritant as well as allergic contact dermatitis both in rodents and in humans. Despite their induction by different mechanisms, they cannot be differentiated by macroscopic appearance and, by histological examination they are both generally characterized by a perivascular mononuclear cell infiltrate and capillary hyperpermeability. Recently, cytokines, a family of inducible glycoproteins that play a pivotal role in immune and inflammatory reactions, have been identified as useful tools for differentiation of irritant and allergic contact dermatitis. In this article the role of cytokines in the development and differentiation of irritant and allergic contact dermatitis is discussed.

Suppression of Experimental Autoimmune Encephalomyelitis by Dermatan Sulfate

The effect of dermatan sulfate (DS) on the treatment of Lewis rats with experimental autoimmune encephalomyelitis (EAE) was examined. DS, a sulfated glycosaminoglycan, has been reported to exhibit anticoagulant and fibrinolytic activities. DS treatment (50 mg/kg/day) facilitates recovery from the clinical manifestations of EAE. In this study, the fibrinolytic activity was higher in DS-treated rats than in saline-treated rats. Although the degree of perivascular mononuclear cell infiltration in the spinal cord was not suppressed in DS-treated rats compared to that in saline-treated rats, perivascular fibrin deposition was markedly suppressed in DS-treated rats. These findings suggest that DS would act as an effective therapeutic agent for EAE by preventing fibrin deposition.

Weak at the knees

A 71-year-old man was referred to hospital in March, 1998, by his general practitioner with a 6-month history of leg weakness. He reported progressive difficulty over 2 months in climbing stairs or rising from a chair without using his arms, and his legs felt numb. He had no difficulty walking on the flat and was otherwise well. His diabetes had been diagnosed when he was aged 58 years; he was changed from oral hypoglycaemics to insulin after 11 years because of poor glycaemic control. He had uncomplicated myocardial infarctions aged 60 and 68, and had a successful transurethral resection of the prostate for benign hypertrophy at age 69. He complained of low lumbar back pain, worsened after exercise or standing for long periods, for the past 10 years. He was taking mixtard insulin, lowdose aspirin, and coproxamol as required. He stopped smoking 20 years ago, and drank 14 units of alcohol weekly. On examination, he was obese. His blood pressure was 140/90 mm Hg. Tone, power, and sensation in his arms were normal but reflexes could only be elicited with reinforcement. No wasting, fasciculation, tenderness, or abnormal tone was found in his legs. Hip flexion and extension, and knee extension were mildly reduced on both sides. He was unable to rise from a squat unaided, but muscle power was normal distally. No leg reflexes were present. Proprioception and vibration sense were absent below his knees. Lumbar lordosis was maintained, but lumbar-spine movements were reduced. He had a smooth, moderately enlarged prostate with normal anal tone and sensation. The rest of the examination, including cranialnerve testing and fundoscopy was normal. Blood tests showed a normal full blood count, urea and electrolytes, liver transaminases, serum vitamin B12 and folate, alkaline phosphatase, calcium, thyroid function, and complement concentration. Random glucose was 9·9 mmol/L, glycosylated haemoglobin 7·3%, erythrocyte sedimentation rate (ESR) 32 mm in the first hour, C-reactive protein 1·3 mg/dL (normal <5 mg/dL), and creatine phosphokinase (CKP) 496 IU/L (normal 24-195 IU/L). He was antinuclear antibody positive 1:80, rheumatoid factor positive 1:80, double stranded DNA and VDRL negative. Urinalysis revealed glucose +, and no protein. His chest radiograph and abdominal ultrasound scan were normal. Computed tomography scan of his lumbar spine showed a degenerative disc at L4/5, with no evidence of root or spinal cord compression. Electromyography (EMG) showed moderate sensory-motor neuropathy, with an active myopathy. A muscle biopsy specimen showed necrosis of muscle fibres with a perivascular mononuclearcell infiltrate. At initial assessment a diagnosis of diabetic amyotrophy (proximal motor neuropathy) with peripheral sensory neuropathy was made. However, the elevated CPK and EMG and muscle-biopsy findings suggested polymyositis as the cause of weakness, with a coincident

Neuropathogenesis of Simian Immunodeficiency Virus in Neonatal Rhesus Macaques

Neonatal human immunodeficiency virus (HIV) infection usually occurs intrapartum or postpartum and results in a higher incidence of neurological dysfunction than is seen in adults. To explore the neuropathogenesis of neonatal HIV infection, we infected neonatal macaques with simian immunodeficiency virus (SIV) and followed the course of infection focusing on early time points. Infected neonates had decreased brain growth and mild histological changes in brain that resembled those seen in pediatric AIDS, including perivascular infiltrates of mononuclear cells, mineralization of vessels in the basal ganglia, and gliosis. The perivascular lesions and gliosis were associated with the presence of occasional infected cells that required in situ hybridization with radiolabeled riboprobes for detection. Using this technique, SIV-infected cells were detected in the brain parenchyma within 7 days of infection. These findings were confirmed by nested PCR for SIVgag DNA in brain and RT-PCR for viral RNA in cerebrospinal fluid. Together, these techniques revealed SIV infection of the CNS in 12 of 13 neonates infected with SIVmac239, 3 of 3 infected with SIVmac251, and 2 of 2 infected with SIVmac239/316. The prevalence of CNS infection was indistinguishable from that of older animals infected with the same dose and stock of virus, but neonates appeared to have fewer infected cells in the CNS and detecting them required more sensitive techniques. This observation was true regardless of inoculum and despite the fact that neonates had equal or greater viral loads in the periphery compared with older animals. These data suggest that maturation-dependent host factors have a major impact on the neuropathogenesis of pediatric AIDS.

Generalized pustular eruptions associated with oral terbinafine.

An active 62-year-old man with noninsulin-dependent diabetes and chronic tinea pedis and tinea unguium developed a painless neurotrophic foot ulcer. His medical history was significant for mild hypercholesterolemia, chronic obstructive pulmonary disease, and long-term tobacco and alcohol use. Oral medications were Glyburide, Glucophage, Zestoretic, gemfibrozil, and aspirin, all of which had been administered daily for at least 8 months. There was no personal or family history of skin disease. After the ulcer failed to respond to conventional therapy, including wound care, debridement, and oral antibiotics, oral terbinafine was prescribed, 250 mg/day, for dermatophytosis-impaired wound healing. After 44 days of terbinafine therapy, the patient developed a generalized, erythematous, maculopapular, pruritic eruption accompanied by fatigue and chills. He denied cough, arthralgias, dizziness, hematuria, or exposure to anyone ill. Despite instructions to stop taking the medication, the patient erroneously continued to take terbinafine. One week later, he was referred to our institution. Physical examination revealed a nontoxic appearing middle-aged man with diffuse, confluent, erythematous plaques studded with pustules, lakes of pus, and crusted erosions and a fever of 38.9 °C ( 1, 2). Palms, soles, and mucous membranes were unaffected, and the groin was relatively spared. Toenails exhibited yellow–white discoloration, subungual debris, and onychauxis. Fingernails were normal. Lymphadenopathy was absent. A 1.3 cm by 1.7 cm superficial, painless ulcer without significant undermining was present on the left sole over the first metatarsophalangeal joint. There was decreased sensation from the toes to the midleg. Pedal pulses were palpable. Figure 1Open in figure viewerPowerPoint Extensive pustular eruption of acute onset involving the trunk and extremities Figure 2Open in figure viewerPowerPoint Erythematous plaques, pustules, lakes of pus, and crusted erosions Laboratory analyses revealed elevated white blood cell count (10.7 × 103 μL) with 11% eosinophils. Electrolytes, renal, thyroid, and liver function tests, urinalysis, and sedimentation rate were normal. A skin biopsy specimen showed an intraepidermal, spongiotic, vesiculopustular dermatitis with a superficial, perivascular, mixed inflammatory cell infiltrate of lymphocytes, neutrophils, and scattered eosinophils ( 3, 4). A periodic acid–Schiff stain was negative for fungi. Figure 3Open in figure viewerPowerPoint Vesiculopustular dermatitis with diffuse superficial perivascular infiltrate (original magnification, ×10) Figure 4Open in figure viewerPowerPoint Subcorneal neutrophilic pustule, perivascular infiltrate of mononuclear cells, neutrophils, and occasional eosinophils (original magnification, ×40) Terbinafine was stopped, but all other medications were continued. Hydrotherapy, twice-daily triamcinolone ointment, and a prednisone taper from 60 mg to 0 mg over 3 weeks were initiated. In 4 days, there was complete resolution of the fever and pustulosis and a significant reduction of the erythema. At 40 days, mildly pruritic, erythematous plaques persisted on the trunk and extremities. The temporal relationship strongly suggested terbinafine as the inciting agent in this patient. Oral provocation test was not performed due to unacceptable patient risk.

Chronic Pruritic Papular Dermatitis in Adult Men: A Variant of Prurigo

Chronic recurrent pruritic papular eruptions in which a specific diagnosis cannot be established becomes a baffling experience to the dermatologist. We have met adult male patients with chronic recurrent pruritic papular eruptions, but their clinicopathological features are not described in English language textbooks. Our purpose was to study the clinical and histological features of this entity and review the various existing taxonomy. We conducted a study of 20 patients over a six year period by taking histories, performing skin biopsies, screening patch tests, and doing immunofluoresence studies. The eruptions occurred exclusively in male adults and had a predilection for the trunk and proximal extremities. The lesions were characterized by severely pruritic, nonfollicular, monomorphic, erythematous urticarial papules. There was no evidence of atopic diathesis or history of insect bite. Most patients had normal levels of serum eosinophils and IgE. The predominant histopathologic finding was a presence of perivascular infiltration of mononuclear cells with eosinophils. The patients followed a chronic course of at least six months with waxing and waning; systemic corticosteroids were the only effective treatment. Finally, all other pruritic erythematous papular dermatoses were ruled out. These cases comprise a distinct entity that has previously been mentioned in a few reports. Clear definition of this entity with an appropriate designation is in order to avoid confusion among dermatologists, and we propose the disease name "chronic papular dermatitis in adult men" as a variant of prurigo.

Morphological correlates of neurological dysfunction in macaques infected with neurovirulent simian immunodeficiency virus.

The pattern of neurological disease caused by human immunodeficiency virus (HIV) infection of the central nervous system (CNS) was investigated using a macaque model of acquired immune defiency syndrome (AIDS). Seven of nine macaques inoculated with neurovirulent simian imunodeficiency virus (SIVmac ) developed AIDS within 3 months. Four of these had clinically obvious neurological disease and extensive conduction defects in the form of latency increases in evoked potential (EP) responses. Neuropathologically, all four animals had disseminated white matter disease in the form of multifocal, perivascular and nodular parenchymal mononuclear cell infiltrates, along with extensive involvement of the cortical grey matter, leptomeninges and intracranial portions of cranial nerves. A brisk multinucleated giant cell (MGC) response was a frequent accompaniment in the affected areas. Three of the animals in this group also showed spongiform vacuolation in the occipital grey matter, a lesion described only rarely in HIV encephalitis. In the remaining three animals, there was only minimal evidence of overt neurological impairment or conduction defects. These animals had only mild to moderate neuropathological changes and lesions were virtually confined to the white matter regions of the brain. MGC responses were rare or absent in the CNS of these animals. Neuropathological findings in this SIVmac model have therefore shown good correlation with the severity of clinical and neurophysiological changes, and are reminiscent of HIV-1 encephalitis. More importantly, white matter involvement was a consistent finding in the affected macaques, regardless of the duration and severity of disease, or type of virus inoculated, suggesting an unusual susceptibility for lentiviral infection in these regions of the macaque CNS.

Gammadelta receptor bearing T cells in scleroderma: enhanced interaction with vascular endothelial cells in vitro.

In view of the documented perivascular mononuclear cell infiltration in the involved organs in scleroderma (SSc) and the reported accumulation of gammadelta-T cells in SSc skin and lung, we evaluated gammadelta-T cell interaction with endothelial cells (EC) in vitro. gammadelta- and alphabeta-T cells were isolated from BPMN of SSc patients with early diffuse disease and of matched control subjects by an immunomagnetic method after stimulation with mycobacterium lysate and interleukin-2 for 2 weeks. Lymphocyte adhesion, proliferation, and cytotoxicity to EC were investigated. SSc gammadelta-T cells adhered to cultured EC and proliferated at higher rates than control cells. Furthermore, significant EC cytotoxicity by SSc gammadelta was seen. The cytotoxicity was blocked by addition of anti-gammadelta-TCR antibody and by anti-granzyme A antibody but not by anti-MHC class I and II antibodies. Expression of granzyme A mRNA was seen in five/five SSc gammadelta-T cells and in one/five control cells. alphabeta-T cells from both SSc and control subjects were significantly less interactive with EC than gammadelta-T cells. The data demonstrate EC recognition by SSc gammadelta-T cells and propose gammadelta-T cells as a possible effector cell type in the immune pathogenesis of SSc.

Like frogs disguised as leaves

It has long been a controversial issue whether infection by Chlamydia trachomatis directly contributes to heart disease or is a bystander simply finding a place to live on atherosclerotic plaques. Molecular mimicry is an important factor in the exacerbation of various infectious diseases, and this appears to be a possible mechanism operating in the case of the C. trachomatis–heart disease link. Kurt Bachmaier and colleagues1xChlamydia infections and heart disease linked through antigenic mimicry. Bachmaier, K. et al. Science. 1999; 283: 1335–1339Crossref | PubMed | Scopus (335)See all References1 in Toronto have discovered that a peptide extracted from mouse heart muscle has sequence homology to outer membrane proteins of several Chlamydia spp. In mice, cardiac myosin-induced myocarditis is linked to CD4+ T-cell recognition of major histocompatibility complex (MHC) class II-associated peptides derived from α-myosin heavy chain. These peptides are known to be conserved between mouse and human heart muscle. All the Chlamydia-derived mimics of these myosin peptides induce inflammatory heart disease in mice, characterized by perivascular and pericardial infiltration of mononuclear cells and fibrotic changes, which looks like human myocarditis. Inflammation is restricted to heart muscle and is not seen in skeletal muscle. The authors suggest that the presence of bacterial DNA also acts as a powerful adjuvant for autoaggressive T cells. This work has shown that Chlamydia infection, which is of high prevalence in western societies, superimposed on a permissive genetic background and combined with associated risk factors, such as smoking, high cholesterol levels, stress and obesity, can indeed be a significant threat to the precipitation of inflammatory heart disease.

Angiocentric CD3(+) T-cell infiltrates in human immunodeficiency virus type 1-associated central nervous system disease in children.

A significant proportion of brain tissue specimens from children with AIDS show evidence of vascular inflammation in the form of transmural and/or perivascular mononuclear-cell infiltrates at autopsy. Previous studies have shown that in contrast to inflammatory lesions observed in human immunodeficiency virus type 1 (HIV-1) encephalitis, in which monocytes/macrophages are the prevailing mononuclear cells, these infiltrates consist mostly of lymphocytes. Perivascular mononuclear-cell infiltrates were found in brain tissue specimens collected at autopsy from five of six children with AIDS and consisted of CD3(+) T cells and equal or greater proportions of CD68(+) monocytes/macrophages. Transmural (including endothelial) mononuclear-cell infiltrates were evident in one patient and comprised predominantly CD3(+) T cells and small or, in certain vessels, approximately equal proportions of CD68(+) monocytes/macrophages. There was a clear preponderance of CD3(+) CD8(+) T cells on the endothelial side of transmural infiltrates. In active lesions of transmural vasculitis, CD3(+) T-cell infiltrates exhibited a distinctive zonal distribution. The majority of CD3(+) cells were also CD8(+) and CD45RO+. Scattered perivascular monocytes/macrophages in foci of florid vasculitis were immunoreactive for the p24 core protein. In contrast to the perivascular space, the intervening brain neuropil was dominated by monocytes/macrophages, microglia, and reactive astrocytes, containing only scant CD3(+) CD8(+) cells. Five of six patients showed evidence of calcific vasculopathy, but only two exhibited HIV-1 encephalitis. One patient had multiple subacute cerebral and brainstem infarcts associated with a widespread, fulminant mononuclear-cell vasculitis. A second patient had an old brain infarct associated with fibrointimal thickening of large leptomeningeal vessels. These infiltrating CD3(+) T cells may be responsible for HIV-1-associated CNS vasculitis and vasculopathy and for endothelial-cell injury and the opening of the blood-brain barrier in children with AIDS.

Chronic active hepatitis induced by Helicobacter hepaticus in the A/JCr mouse is associated with a Th1 cell-mediated immune response.

Helicobacter hepaticus infection in A/JCr mice results in chronic active hepatitis characterized by perivascular, periportal, and parenchymal infiltrates of mononuclear and polymorphonuclear cells. This study examined the development of hepatitis and the immune response of A/JCr mice to H. hepaticus infection. The humoral and cell-mediated T helper immune response was profiled by measuring the postinfection (p.i.) antibody response in serum, feces, and bile and by the production of cytokines and proliferative responses by splenic mononuclear cells to H. hepaticus antigens. Secretory immunoglobulin A (IgA) and systemic IgG2a antibody developed by 4 weeks p.i. and persisted through 12 months. Splenocytes from infected mice proliferated and produced more gamma interferon (IFN-gamma) than interleukin-4 (IL-4) or IL-5 when cultured with H. hepaticus outer membrane proteins. The predominantly IgG2a antibody response in serum and the in vitro production of IFN-gamma in excess of IL-4 or IL-5 are consistent with a Th1 immune response reported in humans and mice infected with Helicobacter pylori and Helicobacter felis, respectively. Mice infected with H. hepaticus developed progressively severe perivascular, periportal, and hepatic parenchymal lesions consisting of lymphohistiocytic and plasmacytic cellular infiltrates. In addition, transmural typhlitis was observed at 12 months p.i. The characterization of a cell-mediated Th1 immune response to H. hepaticus infection in the A/JCr mouse should prove valuable as a model for experimental regimens which manipulate the host response to Helicobacter.