Getting to the guts of HIV pathogenesis.

Two groups have shown that, as in macaques infected with simian immunodeficiency virus (SIV), intestinal CD4(+) T cells are selectively and rapidly depleted in the intestine of HIV-infected patients. Depletion of intestinal CD4(+) T cells occurred at all stages of infection regardless of highly active antiretroviral therapy (HAART). Here we discuss the important implications of these papers for our understanding of HIV pathogenesis, treatment, and vaccine design.

Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival.

Regulatory T (T(reg)) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen-reactive lymphocytes mediated by T(reg) cells; however, definitive evidence that T(reg) cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4(+)CD25(+)FOXP3(+) T(reg) cells in 104 individuals affected with ovarian carcinoma, that human tumor T(reg) cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo.

Dendritic cell subsets differentially regulate angiogenesis in human ovarian cancer.

Angiogenesis is essential for both primary and metastatic tumor growth. Tumor blood vessel formation is complex and regulated by many factors. Ovarian carcinomas have a poor prognosis, often associated with multifocal intraperitoneal dissemination accompanied by intense neovascularization.

Classic AIDS in a sooty mangabey after an 18-year natural infection.

Prevailing theory holds that simian immunodeficiency virus (SIV) infections are nonpathogenic in their natural simian hosts and that lifelong infections persist without disease. Numerous studies have reported that SIV-infected sooty mangabeys (SMs; Cercocebus atys) remain disease free for up to 24 years despite relatively high levels of viral replication. Here, we report that classic AIDS developed after an 18-year incubation in an SM (E041) with a natural SIVsm infection.

Peptides identified through phage display direct immunogenic antigen to dendritic cells.

Dendritic cells (DC) play a critical role in adaptive immunity by presenting Ag, thereby priming naive T cells. Specific DC-binding peptides were identified using a phage display peptide library. DC-peptides were fused to hepatitis C virus nonstructural protein 3 (NS3) while preserving DC targeting selectivity and Ag immunogenicity.

In vivo 1H MRS of brain injury and repair during acute SIV infection in the macaque model of neuroAIDS.

The metabolic response of the rhesus macaque brain during acute simian immunodeficiency virus (SIV) infection was investigated with in vivo (1)H MR spectroscopy. Fifteen rhesus macaques were studied before inoculation, and once or twice after infection. In all, 13/15 macaques had elevations of Cho/NAA at 11-13 days postinoculation (dpi); all 10 macaques measured after 13 dpi had subsequent reduction of this ratio (ANOVA, P < 10(-6)).

Body-composition changes in the simian immunodeficiency virus-infected juvenile rhesus macaque.

Background: Body-composition changes are common in individuals infected with human immunodeficiency virus. The purpose of the present study was to measure, as a model of wasting in acquired immunodeficiency syndrome (AIDS), longitudinal body-composition changes in macaques infected with simian immunodeficiency virus (SIV).

Methods: Twelve juvenile macaques were inoculated with SIVmac239.

A prospective longitudinal in vivo 1H MR spectroscopy study of the SIV/macaque model of neuroAIDS.

Background: The neurological complications of HIV infection remain poorly understood. Clinically, in vivo 1H magnetic resonance spectroscopy (MRS) demonstrates brain injury caused by HIV infection even when the MRI is normal. Our goal was to undertsand the dynamics of cerebral injury by performing a longitudinal in vivo 1H MRS study of the SIV/macaque model of neuroAIDS.

The mucosal immune system and HIV-1 infection.

Recent progress in HIV-1 and SIV pathogenesis has revealed that mucosal tissues, primarily the gastrointestinal tract, are major sites for early viral replication and CD4+ T-cell destruction, and may be the major viral reservoir, even in patients receiving HAART. This is likely attributable to the fact that the majority of mucosal CD4+ T-cells co-expressing chemokine receptors requited for HIV-1 entry, reside in mucosal tissues. Furthermore, the intestinal mucosal immune system is continuously bombarded by dietary antigens, resulting in continual lymphocyte activation, dissemination, and homing of these activated lymphocytes (including CCR5+CD4+ T-cells) throughout mucosal tissues.

[From when on can fungi be identified in nasal mucus of humans?].

Background: Fungal spores are frequent in air and their occurrence in the nasal mucus appears to be a common finding within the adult population, as we were able to show in recent studies. 91,3 % of CRS patients but also healthy controls grew positive fungal cultures out of their nasal mucus. The potential role of fungal elements in nasal mucus for the pathogenesis of CRS, with or without polyposis, is currently investigated intensely and discussed very controversially.

Functional simian immunodeficiency virus Gag-specific CD8+ intraepithelial lymphocytes in the mucosae of SIVmac251- or simian-human immunodeficiency virus KU2-infected macaques.

The vaginal and rectal mucosae are the first line of cellular immune defense to sexually transmitted human immunodeficiency virus type 1 (HIV-1) entry. Thus, intraepithelial lymphocytes (IELs) may be important in the immune response to HIV infection. Here we investigated whether functional IELs in mucosal compartments could be visualized by direct staining with a tetrameric complex specific for the simian immunodeficiency virus (SIV) immunodominant Gag epitope in either separated IEL cells or tissues of macaques infected with SIVmac251.

Proximity between 5-HT secreting enteroendocrine cells and lymphocytes in the gut mucosa of rhesus macaques (Macaca mulatta) is suggestive of a role for enterochromaffin cell 5-HT in mucosal immunity.

The involvement of serotonin (5-hydroxytryptamine; 5-HT) in immunoregulation has been well documented. Gut mucosa is a large reservoir of 5-HT most of which is attributed to gut endocrine cells. In this study, we examined the anatomical relationship among 5-HT immunoreactive cells and T and B lymphocytes in the gut mucosa of rhesus monkeys (Macaca mulatta).

Dynamics of Simian immunodeficiency virus-specific cytotoxic T-cell responses in tissues.

Although the dynamics of human immunodeficiency virus and Simian immunodeficiency virus (SIV)-specific cytotoxic T cells (CTLs) have been well documented in the blood, little is known regarding CTL development in other tissues. In this study, seven Mamu-A*01+ macaques were inoculated with SIVmac. Two macaques were killed at 21 days of infection, and SIV gag p11C tetramer responses were measured in the blood, axillary and mesenteric lymph nodes, spleen, bone marrow, and thymus.

Fungal biodiversity--as found in nasal mucus.

The biodiversity of fungi isolated from the nasal mucus of patients suffering from chronic rhinosinusitis and from healthy persons was monitored over 28 months. Mucus samples were obtained by flushing the noses of patients with saline or by endoscopic sinus surgery. Fungi from mucus were cultivated on agar plates.

[The basidiomycete Schizophyllum commune in paranasal sinuses].

In the last fifty years, only 22 medical cases involving the basidiomycetous fungus Schizophyllum commune were reported. In a period of three years we have examined 270 patients suffering from chronic rhinosinusitis as well as from mycoses (fungus balls) within the paranasal sinuses. Either nasal mucus or fungal concrement from the sinuses were cultured and the resulting cultures identified microscopically.

Simian immunodeficiency virus infection in neonatal macaques.

Children with human immunodeficiency virus infection often have higher viral loads and progress to AIDS more rapidly than adults. Since the intestinal tract is a major site of early viral replication and CD4(+) T-cell depletion in adults, we examined the effects of simian immunodeficiency virus (SIV) on both peripheral and intestinal lymphocytes from 13 neonatal macaques infected with SIVmac239. Normal neonates had more CD4(+) T cells and fewer CD8(+) T cells in all tissues than adults.

Influence of sensitization to inhalative allergens on adenotonsillar disease.

Objective: We sought to determine the influence of IgE-mediated sensitization on adenotonsillar disease in children. We compared follow-up after tonsillectomy/adenoidectomy of atopic and nonatopic children.Study design and setting A prospective study of 293 children consecutively undergoing tonsillectomy/adenoidectomy was conducted at a university hospital center.

Quantitative evaluation of Enterocytozoon bieneusi infection in simian immunodeficiency virus-infected rhesus monkeys.

The association of the microsporidia Enterocytozoon bieneusi with chronic diarrhea and wasting in individuals with acquired immunodeficiency syndrome (AIDS) has been demonstrated. The disease caused by E. bieneusi has been linked to decreased levels of circulating CD4+ T lymphocytes.

Infectious agent and immune response characteristics of chronic enterocolitis in captive rhesus macaques.

Chronic enterocolitis is the leading cause of morbidity in colonies of captive rhesus macaques (Macaca mulatta). This study's aim was to identify the common enteric pathogens frequently associated with chronic enterocolitis in normal, immunocompetent rhesus monkeys and to elucidate the influence of this clinical syndrome on the host immune system. We analyzed the fecal specimens from 100 rhesus macaques with or without clinical symptoms of chronic diarrhea.

[Incidence and detection of fungi and eosinophilic granulocytes in chronic rhinosinusitis].

Background: Chronic Rhinosinusitis (CRS) is the most common chronic disease in the United States. Though for Europe no data are available, we have to assume that the situation is similar. Although the disease is defined very well by clinical symptoms, up to date the etiology and pathogenesis of chronic rhinosinusitis are unknown.

Decreased CCR5 expression on CD4+ T cells of SIV-infected sooty mangabeys.

Sooty mangabeys are the natural host of simian immunodeficiency virus (SIVsm). When injected into rhesus macaques, SIVsm infection results in progressive declines in CD4(+) T cells, opportunistic infections, and AIDS. In contrast, SIV-infected sooty mangabeys do not develop disease and live an apparently normal life span in captivity, despite maintaining high levels of virus in plasma throughout their lives.

Endolacrimal KTP laser-assisted dacryocystorhinostomy.

Objective: To describe our experience with potassium-titanyl-phosphate (KTP) laser-assisted dacryocystorhinostomy, controlled via endolacrimal and endonasal endoscopy. The development of miniendoscopes enables endoscopy of the lacrimal drainage system via the lacrimal puncta to visualize the exact site of a stenosis.

Design: A case series of 78 patients, with 1-year postoperative follow-up.

Vaginal CD4+ T cells express high levels of CCR5 and are rapidly depleted in simian immunodeficiency virus infection.

Worldwide, the majority of human immunodeficiency virus-1 cases occur through heterosexual transmission, yet little is known regarding the phenotype of CD4(+) T cells in the vaginal mucosa. In the present study, lymphocytes were compared from the lymph nodes, blood, and vagina from uninfected and simian immunodeficiency virus (SIV)-infected macaques. In mature female macaques, 54%-67% of the vaginal CD4(+) T cells expressed C chemokine receptor 5 (CCR5), whereas 84%-99% coexpressed CXC chemokine receptor 4.

Characterization of an in vitro rhesus macaque blood-brain barrier.

The blood-brain barrier (BBB) has been modeled in vitro in a number of species, including rat, cow and human. Coculture of multiple cell types is required for the correct expression of tight junction proteins by microvascular brain endothelial cells (MBEC). Markers of inflammation, especially MHC-II, and cell adhesion molecules, such as VCAM-1, are not expressed on the luminal surface of the barrier under resting conditions.

Distribution and immunophenotype of DC-SIGN-expressing cells in SIV-infected and uninfected macaques.

DC-SIGN (dendritic cell-specific ICAM-3 grabbing nonintegrin), an external C-type lectin expressed on dendritic cells (DCs), has been proposed to play a pivotal role in trafficking HIV/SIV from mucosal surfaces to lymphoid tissues. Although the location of DC-SIGN expression has been established in a limited number of human tissues, its distribution in the rhesus macaque has not yet been determined. This study characterized the distribution and immunophenotype of DC-SIGN-expressing cells in SIV-infected and uninfected macaque tissues by immunohistochemistry (IHC) and confocal microscopy.