Begell House Inc.
Critical Reviews™ in Immunology
CRI
1040-8401
27
1
2007
The Ambivalent Nature of T-Cell Infiltration in the Central Nervous System of Patients with Multiple Sclerosis
1-14
10.1615/CritRevImmunol.v27.i1.10
Joris
Vanderlocht
Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
Niels
Hellings
Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
Jerome J. A.
Hendriks
Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
Piet
Stinissen
Hasselt University, Biomedical Research Institute and Transnationale Universiteit Limburg, School of Life Sciences, Diepenbeek, Belgium
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) of presumed autoimmune origin. On the basis of the pathophysiology of MS, inflammatory reactions in the CNS are considered detrimental. Recent evidence suggests that the injured CNS can also benefit from immune activity. In this review, we will first provide an overview of the mechanisms by which immune cells contribute to CNS injury in MS. We will further review evidence supporting a neuroprotective role of CNS inflammation with special focus on the protective properties of autoimmune reactions. Finally, we discuss the proposed mechanisms by which autoreactive T cells exert protection in the CNS and how this protection is regulated.
Mast Cell Homeostasis: A Fundamental Aspect of Allergic Disease
15-32
10.1615/CritRevImmunol.v27.i1.20
John J.
Ryan
Department of Biology, Virginia Commonwealth University, Richmond, VA
Mohit
Kashyap
Department of Biology, Virginia Commonwealth University, Richmond, VA
Daniel
Bailey
Department of Biology, Virginia Commonwealth University, Richmond, VA
Sarah
Kennedy
Department of Biology, Virginia Commonwealth University, Richmond, VA
Kelly
Speiran
Department of Biology, Virginia Commonwealth University, Richmond, VA
Jennifer
Brenzovich
Department of Biology, Virginia Commonwealth University, Richmond, VA
Brian
Barnstein
Department of Biology, Virginia Commonwealth University, Richmond, VA
Carole
Oskeritzian
Department of Biochemistry, Virginia Commonwealth University, Richmond, VA
Gregorio
Gomez
Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA
Mast cells are well known for their role in allergic disease and have recently been implicated in inflammatory disorders, including autoimmune arthritis, multiple sclerosis, and atherosclerosis. Although aberrant mast cell activation is the focus of many studies, much less is known about normal mast cell homeostasis. Because loss of the normal constraints on mast cell activation, proliferation, and survival may be central to disease etiology, understanding these issues warrants attention. This review summarizes the knowledge of mast cell homeostasis controlled by IgE and the regulatory cytokines IL-4, IL-10, and TGF-β1. Because each of these proteins plays an important role in immune responses tied to mast cell-associated disease, this group represents a potential set of factors altered in atopic or autoimmune patients. It is interesting to note, for example, that polymorphisms within each of these factors or their receptors are linked to allergic disease. By first understanding how cytokines and IgE regulate mast cell function and survival, we may then predict how these factors may function in disease onset and progression.
Autoimmune Etiology in Chronic Prostatitis Syndrome: An Advance in the Understanding of This Pathology
33-46
10.1615/CritRevImmunol.v27.i1.30
Virginia Elena
Rivero
Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre, Medina Allende, Ciudad Universitaria, Cordoba, Argentina
Ruben Dario
Motrich
Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre, Medina Allende, Ciudad Universitaria, Cordoba, Argentina
Mariana
Maccioni
Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre, Medina Allende, Ciudad Universitaria, Cordoba, Argentina
Clelia Maria
Riera
Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI-CONICET), Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad Nacional de Cordoba, Haya de la Torre, Medina Allende, Ciudad Universitaria, Cordoba, Argentina
The prostate is the target of many inflammatory and neoplastic disorders that affect men of all ages. Pathological conditions of the prostate gland range from infection of this organ by ascending bacteria from infected urine, to chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) of a still unknown etiology (accompanied with inflammation and lymphocyte infiltration of the gland), to benign hyperplasia and cancer. Patients under 50 years of age usually suffer from CP/CPPS, a chronic inflammatory syndrome characterized by pelvic pain, irritative voiding symptoms, and sexual dysfunction complaints.
In this review, we summarize the current knowledge regarding immunological alterations present in CP/ CPPS patients. Remarkably, an inflammation state, in the absence of an invading infectious agent, is established in these patients, suggesting that an autoimmune process could be involved. In fact, specific autoimmune response to prostate antigens has recently been reported in CP/CPPS patients. Autoimmune response to prostate gland affects the seminal quality reported in these patients and may have critical consequences in their fertility. It is anticipated that preclinical studies in experimental models for CP/CPSS will provide important insights into the etiopathogenic mechanisms involved in this disease. We discuss here the similarities and the differences between human disease and experimental models and argue for the importance of the prostate gland in male reproductive function. Ultimately, we suggest that a state of inflammation, originally incited by an autoimmune response within the prostate, together with a diminished prostate functionality, may compromise male fertility.
MHC-Restricted B-Cell Antigen Presentation in Memory B-Cell Maintenance and Differentiation
47-60
10.1615/CritRevImmunol.v27.i1.40
Michiko
Shimoda
Immunotherapy Center, Department of Pathology, School of Medicine, Medical College of Georgia, 1120 15th St., Augusta, GA 30912
Pandelakis A.
Koni
Immunotherapy Center, Department of Medicine, School of Medicine, Medical College of Georgia, 1120 15th St., Augusta, GA 30912
Memory B-cell development, maintenance, and differentiation have been believed to be tightly regulated by T cells through major histocompatibility complex (MHC)-II-restricted cognate interaction. However, recent studies have indicated that memory B cells are a heterogeneous population with various ontogeny and with derivations from T-cell-independent as well as T-cell-dependent response. In addition, several studies highlight T-cell-independent maintenance and differentiation of memory B cells by innate polyclonal stimuli associated with Toll-like-receptors (TLRs). Thus, both T-cell-dependent and T-cell-independent mechanisms with possibly different physiological functions are required for maximal memory B-cell maintenance and differentiation. In this review, we discuss the mechanisms of memory B-cell maintenance and differentiation by re-examining the requirement for MHC-II-restricted B-cell antigen presentation based on our recent study in a mouse model that lacks MHC-II on memory B cells. We propose that MHC-II-restricted memory B-cell maintenance and differentiation are the indispensable mechanisms by which we achieve health and the maximum quality of memory response with specific antibody production, while preventing plasma cell differentiation from self-reactive memory B cells under the control of T-helper cells and possibly regulatory T cells.
Naturally Occurring Regulatory T Cells: Recent Insights in Health and Disease
61-95
10.1615/CritRevImmunol.v27.i1.50
Giorgio
Raimondi
Thomas E. Starzl Transplantation Institute and Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Michael S.
Turner
Departments of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
Angus W.
Thomson
Thomas E. Starzl Transplantation Institute and Departments of Surgery and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Co-senior authors
Penelope A.
Morel
Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Co-senior authors
Development of naturally occurring CD4+CD25+ T regulatory cells (Treg) in the thymus requires the transcription factor Foxp3. Major histocompatibility complex (MHC) class II, self-ligands expressed by epithelial cells, and thymic stromal lymphopoietin also appear to play important roles. In addition, several molecular regulators of T-cell receptor (TCR) signaling (both positive and negative) have been implicated in the control of Treg development. Foxp3 is a transcriptional repressor of IL-2 and other cytokines and appears to maintain the anergic and suppressor function of these cells. Multiple cell types (T cells, B cells, dendritic cells [DC], and natural killer [NK] cells) are targeted by Treg using diverse suppressor mechanisms, whereas factors that regulate Treg proliferation and function, including Toll-like receptor (TLR) ligands, have also been identified. Because Treg play an important role in the control of autoimmunity, therapeutic strategies are being pursued to enhance their numbers and function in specific autoimmune diseases. In transplantation, where Treg also offer potential for therapy of rejection and graft-versus-host disease (GVHD), indirect allorecognition may be the dominant pathway for immune regulation by these cells. In tumor immunology, Treg have emerged as major suppressors of T-cell-mediated antitumor responses and represent a significant obstacle to effective anticancer vaccines. Strategies aimed at depletion/functional inhibition of these cells by molecular targeting must maintain a critical balance between tumor immunity and self-tolerance.