Begell House Inc.
Critical Reviews™ in Immunology
CRI
1040-8401
18
3
1998
Expression of T Lymphocyte Adhesion Molecules: Regulation During Antigen-Induced T Cell Activation and Differentiation
153-184
10.1615/CritRevImmunol.v18.i3.10
Morris O.
Dailey
Departments of Pathology and Microbiology and the Interdisciplinary Graduate Program in Immunology, The University of Iowa College of Medicine, Iowa City, Iowa.
lymphocyte adhesion
lymphocyte traffic
inflammation
selectins
integrins
endothelium.
The pattern of lymphocyte traffic and migration in vivo is a composite of constitutive recirculation and transient changes induced by interaction with antigen. Naive T lymphocytes in their basal, unstimulated state continuously recirculate throughout the entire host, poised to react to specific antigens that they are programmed to recognize. After interaction with antigen, T cell traffic changes, first with the trapping of reactive cells in antigen-containing lymphoid tissue. Subsequently, the effector cells responding to antigen, accompanied by nonspecific T cells and monocytes, traffic in large numbers to sites of antigen localization, resulting in the localized inflammatory response. Then, as the immune response wanes, memory T cells develop, many of which exhibit still different routes of recirculation. The traffic and tissue localization of leukocytes is regulated by a series of cell surface adhesion molecules that recognize specific ligands on endothelial cells and in the extracellular matrix. Modulation of the expression of these adhesion molecules results in the changes in T cell traffic that are characteristic of each stage of T cell differentiation. Thus, during T cell activation and differentiation, the down-regulation of adhesion receptors specific for lymphoid tissue endothelium and up-regulation of integrins facilitate the targeting of effector cells to sites of inflammation. Subsequent changes in adhesion receptors regulate the traffic of the antigen-specific memory cells. T cell adhesion molecule expression is therefore regulated as a function of the stage of activation and differentiation and, in addition, is influenced by cytokines and the local lymphoid microenvironment.
IL-2-lnduced Cellular Events
185-220
10.1615/CritRevImmunol.v18.i3.20
Javier
Gomez
Department of Immunology and Oncology, Centra Nacional de Biotecnologia, Universidad Autonoma, Campus de Cantoblanco, E-28049, Madrid, Spain
Ana
Gonzalez
Department of Immunology and Oncology, Centra Nacional de Biotecnologia, Universidad Autonoma, Campus de Cantoblanco, E-28049, Madrid, Spain
Carlos
Martinez-A.
Department of Immunology and Oncology, Centra Nacional de Biotecnologia, Universidad Autonoma, Campus de Cantoblanco, E-28049, Madrid, Spain
Angelita
Rebollo
Department of Immunology and Oncology, Centra Nacional de Biotecnologia, Universidad Autonoma, Campus de Cantoblanco, E-28049, Madrid, Spain
IL-2
IL-2 receptor
apoptosis
proliferation
GTP-binding proteins
bcl-2.
In this review we discuss several molecules that are attractive candidates as transducing molecules involved in signaling processes. IL-2 receptor signaling is a complex process involving a large number of molecules: Ras, Rho, PI3 kinase, PKC, Akt, transcription factors NF-AT, and NF-kB and some target genes such as bcl-2, c-myc, c-jun and c-fos. Ras and Rho have been defined as dual molecules because Ras- and Rho-initiated signals can either promote or inhibit apoptosis.
Several studies have contributed to the delineation of a signaling pathway structured in three independent channels designated channels 1, 2, and 3. These three channels serve as major landmarks: Lck-c-fos/c-jun (channel 1), Syk-myc (channel 2), and a pathway leading to actin organization/bcl-2 expression (channel 3). The detailed hierarchical organization of these three channels is presented throughout the review and the model is depicted in the figure.
Expression and Function of Recombination Activating Genes in Mature В Cells
221-235
10.1615/CritRevImmunol.v18.i3.30
Hitoshi
Ohmori
Department of Biotechnology, Faculty of Engineering, Okayama University, Tsushima-Naka, Okayama 700, Japan
Masaki
Hikida
Department of Biotechnology, Faculty of Engineering, Okayama University, Tsushima-Naka, Okayama 700, Japan
recombination activating gene
mature B cell
receptor editing
V(D)J rearrangement
germinal center.
Recombination activating genes, RAG-1 and RAG-2, encode proteins that catalyze the rearrangement of immunoglobulin genes in B cells and T cell receptor genes in T cells to generate the diversity of these important recognition molecules in immune system. It has been believed that these gene rearrangements occur exclusively in premature stages of B and T lymphocytes, consistent with the observation that RAG expression is downregulated in mature lymphocytes. However, recent studies have revealed that even mature B cells in peripheral lymphoid tissues can reexpress RAG-1 and RAG-2 proteins following immunization. Strikingly, RAG-expressing B cells are localized in the germinal centers (GCs) of secondary lymphoid tissues in which somatic hypermutations, isotype switching, and affinity maturation of antibodies take place. Recently, it has been shown that RAG proteins thus induced are functional and can mediate the secondary rearrangement of Ig genes (receptor editing) at mature stages of B cells. Evidence is accumulating suggesting that GCs are regarded as a primary lymphoid tissue. In the present review, we briefly summarize recent advances in the expression and the characterization of RAG proteins and discuss their possible role in mature B cells in relation to the diversification and the selection of B cell repertoire in GCs.
Intraepithelial Lymphocytes: Origins, Distribution, and Function
237-254
10.1615/CritRevImmunol.v18.i3.40
Kenneth
Beagley
Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia
Alan J.
Husband
Department of Veterinary Pathology, Faculty of Veterinary Science, University of Sydney, New South Wales 2006, Australia
intraepithelial lymphocyte
intestine
extra-thymic
cytokine
cytotoxicity
T cell receptor
Intraepithelial lymphocytes (IEL) are associated with the intestinal tract, respiratory tract, genitourinary tract epithelium, and the skin and are the first immune system cells to encounter pathogens that have invaded an epithelial surface. IEL are predominantly T cells (CD3+) with CD8+ cells predominating at most, but not all, sites. Both TCRαβ+ and TCRγδ+ cells are found within IEL populations and an increasing body of evidence suggests that some IEL may arise extrathymically. The presence within intestinal IEL of cells expressing potentially self-reactive TCR suggests that T cell selection within epithelia may differ from thymic T cell selection although recent evidence suggests that these cells may in fact be nonresponsive. IEL exhibit various cytotoxic activities including alloreactive and virus-specific CTL activity, NK activity and spontaneous cytotoxicity, activities consistent with an immune surveillance or first line of defence role. IEL also appear activated in vivo and secrete a variety of cytokines. Subsets of IEL have been shown to provide B cell help, to play a role in the maintenance of oral tolerance and to regulate epithelial cell function. In this review the morphology, distribution and phenotype of IEL, the potential for extrathymic development and possible functions of this unique lymphoid population are discussed.
Proteases and Cell-Mediated Cytotoxicity
255-273
10.1615/CritRevImmunol.v18.i3.50
Alison J.
Darmon
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1P 8BT, U.K.
R. Chris
Bleackley
Department of Biochemistry, Medical Sciences Building, University of Alberta, Edmonton, Alberta T6G 2H7, Canada
apoptosis
granzymes
death receptors
ICE/Ced-3 proteases
caspases.
Cytotoxic T lymphocytes and natural killer cells represent the body’s primary defense against viral-infected and tumorigenic cells. The classically described mechanism by which these cells induce target cell death is granule mediated: cytolytic granules within the killer cell are directionally exocytozed toward the target cell, and the granule contents inflict a "lethal hit" on the target cell. A second mechanism of cytotoxicity is now known to exist, and utilizes cell surface receptors on the target cell, for which the ligand is expressed on the killer cell. Receptor oligomerization results in the recruitment of cytoplasmic proteins to the receptors and the transduction of a death signal to the target cell. In both granule- and receptor-mediated cytotoxicity, the target cell dies through a defined series of steps, which together are termed apoptosis. Recent work on apoptosis has defined a family of cysteine proteases, the caspases, which appear to be involved in the initiation of apoptosis in response to a number of stimuli. This review focuses on studies that link these proteases to target cell death induced by cytotoxic cells.