Begell House Inc.
Critical Reviews™ in Immunology
CRI
1040-8401
23
5-6
2003
Features and Functions of gd T Lymphocytes: Focus on Chemokines and Their Receptors
32
10.1615/CritRevImmunol.v23.i56.10
Dieter
Kabelitz
Institute of Immunology, University of Kiel, Kiel, Germany
Daniela
Wesch
Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany
gd T cells are a distinct subgroup of T lymphocytes that are enriched at certain anatomical localizations, such as the small intestinal epithelia and other epithelia. gd T cells recognize microbial antigens, such as heat shock proteins (in mice) or phosphorylated bacterial metabolites (in humans), and control the integrity of epithelia. At the effector cell level, they share with the conventional gd T lymphocytes potent cytotoxic activity and the capacity to produce a variety of cytokines, including specific cytokines such as keratinocyte growth factor. Here we summarize the current knowledge on the role of chemokines and their receptors in the migration and function of gd T cells. As an example, the migration of gd T cells to the small intestine is guided by the chemokine receptor CCR9 and the local expression of the corresponding ligand CCL25 (also termed thymus-expressed chemokine, TECK). Chemokine receptor expression also correlates with the functional program of T cells. In this respect, the strong expression of the MIP-1a/MIP-1b/RANTES (CCL3/CCL4/CCL5)-receptor CCR5 correlates with a T-helper 1 phenotype of human Vg9Vd2-expressing gd T cells. The regulation of chemokine receptors, together with the pattern of local chemokine production, plays an important role in the localization of gd T cells under physiological and pathophysiological conditions, such as infection, inflammation, and tumor defense.
Shigellosis: Innate Mechanisms of Inflammatory Destruction of the Intestinal Epithelium, Adaptive Immune Response, and Vaccine Development
32
10.1615/CritRevImmunol.v23.i56.20
P. J.
Sansonetti
Unite de Pathogenie Microbienne Moleculaire, INSERM U389, Institut Pasteur, 28 Rue du Dr Roux, 75015 Paris, France
Armelle
Phalipon
Unite de Pathogenie Microbienne Moleculaire, INSERM U389, Institut Pasteur, 28 Rue du Dr Roux, 75015 Paris, France
Acute infectious colitis remains a major pediatric issue of worldwide impact because it still represents a significant public health burden among the larger group of diarrheal diseases with the highest mortality rate. It is also a relevant model of inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis. Among cases of acute colitis of infectious origin, shigellosis is certainly the one that has benefited the most from a significant research effort. Shigella, the causative agent, is a Gram-negative bacterium that has the capacity to invade, disrupt, and cause inflammatory destruction of the intestinal epithelial barrier. The molecular and cellular bases of this invasive phenotype essentially encompass crossing of the epithelial lining, apoptotic killing of macrophages, entry into epithelial cells, and escape into the cytoplasm, followed by cell-to-cell spread. Intracellular colonization is likely to protect the micro-organisms from killing by humoral and cellular effectors of the innate immune response. Concurrently, the capacity of Shigella to reprogram invaded epithelial cells to produce proinflammatory mediators plays a major role in the strong inflammatory profile of the disease. This profile is likely to impact on the nature and quality of the adaptive response, which is dominated by humoral protection at the mucosal level.
CD1d-Mediated Antigen Presentation to Natural Killer T (NKT) Cells
18
10.1615/CritRevImmunol.v23.i56.30
Randy R.
Brutkiewicz
Department of Microbiology and Immunology, Indiana University School of Medicine, The Walther Oncology Center, Building R2, Room 302, 950 W. Walnut St., Indianapolis, IN 46202-5181
Yinling
Lin
Department of Microbiology and Immunology, Indiana University School of Medicine, and The Walther Oncology Center, Indianapolis, IN 46202; and The Walther Cancer Institute, Indianapolis, IN 46208
Sungyoo
Cho
Department of Microbiology and Immunology, Indiana University School of Medicine, and The Walther Oncology Center, Indianapolis, IN 46202; and The Walther Cancer Institute, Indianapolis, IN 46208
Yu Kyeong
Hwang
Department of Microbiology and Immunology, Indiana University School of Medicine, and The Walther Oncology Center, Indianapolis, IN 46202; and The Walther Cancer Institute, Indianapolis, IN 46208
Venkataraman
Sriram
Department of Microbiology and Immunology, Indiana University School of Medicine, and The Walther Oncology Center, Indianapolis, IN 46202; and The Walther Cancer Institute, Indianapolis, IN 46208
Tonya J.
Roberts
Department of Microbiology and Immunology, Indiana University School of Medicine, and The Walther Oncology Center, Indianapolis, IN 46202; and The Walther Cancer Institute, Indianapolis, IN 46208
CD1d molecules are lipid antigen-presenting molecules. They are involved in presenting these antigens to a unique subpopulation of T cells called natural killer T (NKT) cells, which have the capacity to produce both T helper (Th) 1 and Th2 cytokines. Thus, it is possible that the antigens presented by CD1d and/or the level at which they are presented could have profound effects on the immunoregulation of autoimmune and infectious diseases, as well as cancer. Because of the ability of CD1d-binding ligands to modulate NKT cell responses, targeting CD1d-mediated antigen presentation as a novel approach for new therapies in these and other diseases holds great promise.
A Cell Death Pathway Induced by Antibody-Mediated Cross-Linking of CD45 on Lymphocytes
20
10.1615/CritRevImmunol.v23.i56.40
Ann-Muriel
Steff
MetrioGene Biosciences Inc., 6100 Royalmount Av., Montreal, QC, Canada, H4P 2R2
Marylene
Fortin
MetrioGene Biosciences Inc., 6100 Royalmount Av., Montreal, QC, Canada, H4P 2R2
Fabianne
Philippoussis
MetrioGene Biosciences Inc., 6100 Royalmount Av., Montreal, QC, Canada, H4P 2R2
Sylvie
Lesage
Centre de Recherche du CHUM, Laboratoire d’Immunoregulation, Universite de Montreal, 1560 Sherbrooke E, Montreal, QC, Canada, H2L 4M1
Chantal
Arguin
MetrioGene Biosciences Inc., 6100 Royalmount Av., Montreal, QC, Canada, H4P 2R2
Pauline
Johnson
Department of Microbiology and Immunology, University of British Columbia, Canada
Patrice
Hugo
MetrioGene Biosciences Inc., 6100 Royalmount Av., Montreal, QC, Canada, H4P 2R2
The protein tyrosine phosphatase CD45 is a highly expressed glycoprotein present on all nucleated cells of hematopoietic origin. To date, all the functions attributed to CD45 are inherently coupled to its phosphatase activity. For instance, the regulation of lymphocyte antigen receptor signaling is mediated through the dephosphorylation, and hence activation, of Src-family kinases by CD45. Moreover, signaling via cytokine receptors is negatively modulated by CD45 by dephosphorylation of Janus kinase family members. Recently, another function for CD45, unrelated to regulation of surface receptor signaling, has been unraveled. Specific engagement of CD45 by monoclonal antibodies at the surface of lymphocytes induced their death, through an alternative caspase-independent pathway. In striking contrast to all other previously reported functions for CD45, its phosphatase activity is completely dispensable for the induction of cell death. This article reviews the current knowledge on the death pathway triggered by CD45 ligation on lymphocytes. In an attempt to better elucidate the mechanism of cell death induction through CD45, we also provide original data regarding the susceptibility of various subsets of immature and mature T and B cells to death induced by CD45 engagement. The physiological significance and therapeutic potential of CD45-induced death are also discussed.
Major Histocompatibility Lineages and Immune Gene Function in Teleost Fishes: The Road Not Taken
32
10.1615/CritRevImmunol.v23.i56.50
Rene J. M.
Stet
Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, Wageningen, The Netherlands
Corine P.
Kruiswijk
Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, Wageningen, The Netherlands
Brian
Dixon
Department of Biology, University of Waterloo, Waterloo, Ontario, Canada
It has become increasingly clear over the course of the past decade that the immune system genes of teleosts and tetrapods are plainly derived from common ancestral genes. The last 5 years, however, have also made it abundantly clear that in the teleost genome some of these genes are organized in a manner very different from that seen in mammals. These differences are probably the result of differences in life history traits, such as fecundancy, within each group of species when faced with an evolutionary fork in the road shortly after their divergence from each other. One group, the tetrapods, including mammals, chose a highly organized linked major histocompatibility complex, while in teleosts the major histocompatibility genes remained unlinked. In this review we will discuss the structural and functional implications of this different organization, particularly for major histocompatibility genes, but drawing on the current knowledge of some other genes for further support for the hypothesis that each group took a different road, one more traveled and one less taken.
Compartmentalization g/d T Cells and Their Putative Role in Mucosal Immunity
16
10.1615/CritRevImmunol.v23.i56.60
Wolfgang
Holtmeier
Medizinische Klinik II, Division of Gastroenterology, Johann Wolfgang Goethe-Universitat, 60590 Frankfurt am Main, Germany
g/d T cells are an enigmatic group of cells and their functions still remain unknown. The epithelialassociated g/d T cells, which are abundant at mucosal surfaces, are ideally situated to contribute to the initial stages of the immune response. Recent evidence suggests that they recognize stress-induced self-antigens which would enable a homogenous population of g/d T cells to monitor multiple insults to the epithelium. This could explain the observed oligoclonality and homogenous distribution of cells carrying identical TCR within mucosal surfaces. However, the analysis of the TCR d repertoire from different mucosal surfaces indicated that g/d T cells are highly compartmentalized. Thus, g/d T cells are not one homogenous group of cells which recognize the same (stressinduced) self-antigens, but consist of different subsets that are likely to have distinct functions. It is possible that g/d T cells interact with antigens that are specific for that organ or recognize foreign antigens which are limited to that site. In addition it was shown that g/d T cells can have opposite functions and be proinflammatory or promote epithelial healing. This review focuses on the distribution and repertoire of mucosal g/d T cells and discusses what is currently known about the functions of these cells. Furthermore, their potential role in inflammatory bowel disease is examined.