Composition Of Cellular Infiltrate Research Articles

Revolutionizing Cancer Immunology: The Power of Next-Generation Sequencing Technologies.

It has long been appreciated that tumors are diverse, varying in mutational status, composition of cellular infiltrate, and organizational architecture. For the most part, the information embedded in this diversity has gone untapped due to the limited resolution and dimensionality of assays for analyzing nucleic acid expression in cells. The advent of high-throughput, next-generation sequencing (NGS) technologies that measure nucleic acids, particularly at the single-cell level, is fueling the characterization of the many components that comprise the tumor microenvironment (TME), with a strong focus on immune composition. Understanding the immune and nonimmune components of the TME, how they interact, and how this shapes their functional properties requires the development of novel computational methods and, eventually, the application of systems-based approaches. The continued development and application of NGS technologies holds great promise for accelerating discovery in the cancer immunology field.

Composition of the cellular infiltrate in patients with simple and complex appendicitis

BackgroundIt is now well established that there are two types of appendicitis: simple (nonperforating) and complex (perforating). This study evaluates differences in the composition of the immune cellular infiltrate in children with simple and complex appendicitis. Materials and methodsA total of 47 consecutive children undergoing appendectomy for acute appendicitis between January 2011 and December 2012 were included. Intraoperative criteria were used to identify patients with either simple or complex appendicitis and were confirmed histopathologically. Immune histochemical techniques were used to identify immune cell markers in the appendiceal specimens. Digital imaging analysis was performed using Image J. ResultsIn the specimens of patients with complex appendicitis, significantly more myeloperoxidase positive cells (neutrophils) (8.7% versus 1.2%, P < 0.001) were detected compared to patients with a simple appendicitis. In contrast, fewer CD8+ T cells (0.4% versus 1.3%, P = 0.016), CD20 + cells (2.9% versus 9.0%, P = 0.027), and CD21 + cells (0.2% versus 0.6%, P = 0.028) were present in tissue from patients with complex compared to simple appendicitis. ConclusionsThe increase in proinflammatory innate cells and decrease of adaptive cells in patients with complex appendicitis suggest potential aggravating processes in complex appendicitis. Further research into the underlying mechanisms may identify novel biomarkers to be able to differentiate simple and complex appendicitis.

The composition of cellular infiltrates in anti-HMG-CoA reductase-associated myopathy.

To characterize cellular infiltrates in muscle biopsies from patients with anti-3-hydroxy-3-methyl-gulatryl-CoA reductase (HMGCR)-associated myopathy. Biopsies from 18 anti-HMGCR myopathy and 7 control dermatomyositis patients were analyzed. CD4+ and CD8+ T-cells were scattered within the endomysium in 50% of anti-HMGCR biopsies. All anti-HMGCR biopsies included increased endomysial and/or perivascular CD163+ M2 macrophages; CD11c+ M1 macrophages were present in 18.8%. CD123+ plasmacytoid dendritic (PD) cells were observed within the endomysium and perivascular spaces in 62.5% of anti-HMGCR biopsies. Membrane attack complex was deposited on endothelial cells in 50% and on the sarcolemma of nonnecrotic muscle fibers in 85.7% of anti-HMGCR cases. Major histocompatibility complex class I antigen was up-regulated in 87.5% of the anti-HMGCR cases. In addition to necrosis, scattered CD4+, CD8+, and PD cells are characteristic of anti-HMGCR myopathy. Predominant M2 polarization suggests infiltrating macrophages are more likely to be involved with tissue repair than destruction.

Composition of Cellular Infiltrates in the Intestine of Patients with Common Variable Immunodeficiency (CVID)

Composition of Cellular Infiltrates in the Intestine of Patients with Common Variable Immunodeficiency (CVID)

Clinical and immunologic variables in skin of patients with atopic eczema and either positive or negative atopy patch test reactions

Background: Epicutaneous application of aeroallergens induces a positive atopy patch test (APT) response in about 50% of patients with atopic eczema (AE) and sensitization for these allergens. Objective: To elucidate the mechanisms determining the outcome of the APT, the following questions were addressed. Are there differences in clinical features between patients with AE who have positive versus negative APT responses? Is a macroscopically negative APT response also histologically negative, and if so, are there differences in clinically noninvolved skin between the two groups regarding (1) the sensitivity toward an irritant, (2) the composition of cellular infiltrate, (3) the presence of aeroallergen-specific T cells, and (4) the number of IgE+ cells? Methods: Punch biopsy specimens from both house dust mite patch tested and the clinically noninvolved skin of patients with AE who have positive APT responses (n = 10) and negative APT responses (n = 10) and those from the normal skin of atopic individuals without AE (n = 10) and nonatopic volunteers (n = 10) were analyzed by using immunohistochemistry with mAbs against eosinophil cationic protein, IgE, the high-affinity receptor for IgE, and CD3 and CD25 mAbs. Furthermore, T-cell lines were propagated from noninvolved skin of all patient and control groups. The T-cell lines were tested for house dust mite specificity. Results: Negative APT sites were immunohistochemically similar to clinically noninvolved AE skin. There were no significant differences between patients with AE who had positive and negative APT results regarding either clinical features, the composition of cellular infiltrate, or the presence of allergen-specific T cells in clinically noninvolved skin. However, differences were observed regarding the presence of IgE on epidermal CD1a+ cells. Conclusion: Our results indicate that a positive APT reaction requires the presence of epidermal IgE+ CD1a+ cells in clinically noninvolved skin, but that also other, as yet unknown, discriminatory factors are involved. (J Allergy Clin Immunol 2000;105:1008-16.)

Atopy patch testing--a diagnostic tool?

Atopy patch testing--a diagnostic tool?

The Conjunctiva in Acute and Chronic Mucous Membrane Pemphigoid: An Immunohistochemical Analysis

The mechanism of chronic progressive conjunctival cicatrization in mucous membrane pemphigoid is not well understood, and current therapy is often of limited use. Rapid progression of cicatrization follows exacerbations of clinical inflammation, and the investigation of immune mechanisms related to disease activity may provide a clue for more effective therapeutic strategies. The authors undertook an immunohistochemical study, using monoclonal and polyclonal antibodies in glycol methacrylate-embedded tissues, of epibulbar conjunctival biopsy specimens obtained from 20 patients with ocular cicatricial pemphigoid and from 12 matched healthy controls. The study patients were classified according to the ocular disease activity as acute ulcerative (n = 4), subacute (n = 8), and chronic (n = 8). The composition of the subepithelial cellular infiltrate varied with disease activity. Acute disease was characterized by an abundance of macrophages and neutrophils. The number of T lymphocytes was significantly raised in all the disease groups, but were most marked in subacute disease. Of the T-cell subsets, there were more CD8- than CD4-positive cells observed, except in acute disease where there were equal numbers. Only approximately 5% of the T cells in all disease groups were activated as demonstrated by expression of interleukin-2 receptor. There was increased expression of major histocompatibility complex class II (MHC II) molecules on macrophages, fibroblasts, and other cells in all the groups. The number of B cells and natural killer cells was not increased. Staining for the fibrogenic cytokines, transforming growth factor-beta (TGF-beta), platelet-derived growth factor, and basic fibroblast growth factor was found in both pemphigoid patients and control persons, but the intensity of TGF-beta staining was significantly greater in acute disease. The composition of the cellular infiltrate in the bulbar conjunctiva depends on clinical disease activity. The numbers of neutrophils and macrophages seem to reflect clinical disease activity. Fibrogenic cytokines, especially TGF-beta, may play an important role in the formation of conjunctival scar tissue.

Similarities between the Forssman carotid syndrome and experimental allergic encephalomyelitis.

The Forssman carotid syndrome was induced in guinea pigs to study the mechanism of demyelination-like lesions in this animal model and to compare it with experimental allergic encephalomyelitis days after intracarotid injection of rabbit anti-Forssman antibody and chronic lesions at 7-21 days post injection, using routine histological, immunofluorescent, and electron-microscopic techniques. The results were compared to those in a group of guinea pigs with acute or chronic lesions of EAE. The picture was remarkably similar in the two conditions, in regard to localization in the central nervous system (CNS), composition of cellular infiltrates, diameter of lesions produced, myelin loss and axonal degeneration, together with gamma globulin deposition in small vessels in affected areas. The differences were that in the Forssman carotid syndrome, in contrast to EAE, there were no mononuclear cell infiltrates in the acute phase, and no evidence of macrophages invading myelin sheaths was detected. Perivascular lesions consisted of demyelination within infiltrates of mono-nuclear cell in chronic relapsing EAE, but not in the Forssman carotid syndrome. It is suggested that investigation of the CNS may be of benefit in the pathogenetic study of demyelinating disease.

Composition of cellular infiltrates in rejected human corneal allografts.

We utilized the leu series of monoclonal antibodies and an indirect immunoperoxidase technique to quantitate the cellular infiltrates in seven rejected human corneal allografts and compared them to nine identically processed corneas from patients with chronic herpetic stromal keratitis and to three control corneas. The cellular infiltrates in the rejected allografts were of mixed composition, comprised predominantly of leu-1 positive T-lymphocytes and leu-M3 positive macrophages. Both helper and cytotoxic-suppressor T-cells were identified in the stromal lesions. Statistically significant differences were noted in the absolute number of mononuclear cells and macrophages seen infiltrating the rejected corneal allografts compared to the herpetic corneas. We discuss the implications of these findings with regard to possible mechanisms underlying corneal allograft rejection in man.