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Lymph Node T Cells (lymph + node_t_cell)

Distribution by Scientific Domains
Medical Sciences100%

Selected Abstracts

Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2004
Lars Helgeland
Abstract Two populations of CD8+ IEL generally express restricted, but apparently random and non-overlapping TCR repertoires. Previous studies in mice suggested that this could be explained by a dual origin of CD8+ IEL, i.e. that CD8,,+ IEL derive from a few peripheral CD8+ T cell lymphoblasts stimulated by microbial antigens in gut-associated lymphoid tissue, whereas CD8,,+ IEL descend from an inefficient intestinal maturation pathway. We show here that the gut mucosa, instead, becomes seeded with surprisingly broad and generally non-overlapping CD8 IEL repertoires and that oligoclonality is induced locally after microbial colonization. In germ-free (GF) rats, both CD8,,+ and CD8,,+ IEL displayed surprisingly diverse TCR V, repertoires, although ,-chain diversity tended to be somewhat restricted in the CD8,,+ subset. CDR3 length displays in individual V,-C, and V,-J, combinations generally revealed polyclonal distributions over 6,11 different lengths, similar to CD8+ lymph node T cells, and CDR3, sequencing provided further documentation of repertoire diversity. By contrast, in ex-GF rats colonized with normal commensal microflora, both CD8,,+ and CD8,,+ IEL displayed oligoclonal CDR3 length distributions for most of the V, genes analyzed. Our data suggest that microbial colonization induces apparently random clonal expansions of CD8,,+ and CD8,,+ IEL locally in the gut. [source]

THIS ARTICLE HAS BEEN RETRACTED STEALTH matters: a novel paradigm of durable primate allograft tolerance

IMMUNOLOGICAL REVIEWS, Issue 1 2001
J. M. Thomas
Summary: We review a novel strategy for tolerance induction developed in rhesus macaques and termed STEALTH. We summarize the evolution of the STEALTH model, the results of successful trials in inducing long-term, stable transplant tolerance in rhesus kidney and diabetic islet recipients and discuss information related to the mechanism by which durable tolerance is induced. STEALTH tolerance is induced by a 3-day treatment course of CD3, immunotoxin (IT) combined with a 14-day treatment with deoxyspergualin (DSG). IT causes profound depletion of sessile lymph node T cells as well as the more accessible circulating T cells. DSG, an inhibitor of HSC 70-mediated NF-,B nuclear translocation, arrests maturation of myeloid dendritic cells, blocks production of proinflammatory cytokines induced by IT administration, and promotes systemic production of Th2 type cytokines that persist indefinitely. Such Th2 cytokine deviation has not been reported in NHP transplant recipients. These studies provide proof of principle in a preclinical model that prevention of both acute and chronic allograft rejection, for at least 2.2,4.9 years of follow-up, can be achieved in NHP in the absence of chronic immunosuppressive drugs or other interventions. This strategy for inducing NHP tolerance is discussed in relation to current tolerance paradigms. [source]

Definitive engagement of cytotoxic CD8 T cells in C protein,induced myositis, a murine model of polymyositis

ARTHRITIS & RHEUMATISM, Issue 10 2010
Takahiko Sugihara
Objective To substantiate a pathogenic role of cytotoxic CD8 T cells in the development of a murine polymyositis model, C protein,induced myositis (CIM). Methods Beta2 -microglobulin,null mutant, perforin-null mutant, and wild-type (WT) C57BL/6 mice were immunized with skeletal muscle C protein fragments to provoke CIM. Regional lymph node CD8 or CD4 T cells stimulated with C protein,pulsed dendritic cells were transferred adoptively to naive mice. Inflammation and damage of the muscle tissues were evaluated histologically. Results The incidence of myositis development was significantly lower in ,2 -microglobulin,null and perforin-null mutant mice compared with WT mice. Inflammation was less severe in mutant mice, and the incidence of muscle injury was reduced significantly. Adoptive transfer of lymph node T cells from mice with CIM induced myositis in naive recipient mice. The CD8 T cell,induced muscle injuries were significantly more severe than the CD4 T cell,induced muscle injuries. Conclusion Perforin-mediated cytotoxicity by CD8 T cells is definitively responsible for muscle injury in CIM. [source]

Indoleamine 2,3 dioxygenase,mediated tryptophan catabolism regulates accumulation of Th1/Th17 cells in the joint in collagen-induced arthritis

ARTHRITIS & RHEUMATISM, Issue 5 2009
Gabriel Criado
Objective Indoleamine 2,3 dioxygenase (IDO) is a catabolic enzyme that initiates the kynurenine pathway of tryptophan degradation and has immunomodulatory properties. The aim of this study was to investigate the regulation of collagen-induced arthritis by tryptophan catabolism mediated by IDO. Methods Arthritis was induced by immunization with type II collagen. After induction of arthritis, the expression of IDO was analyzed by quantitative reverse transcription,polymerase chain reaction. The effect of IDO deficiency on collagen-induced arthritis was assessed in vivo by administration of 1-methyltryptophan and clinical and histologic evaluation of IDO-deficient mice. The requirement for IDO activation was bypassed by administration of L -kynurenine. Results IDO was induced in lymph node dendritic cells after collagen immunization. Systemic inhibition of tryptophan catabolism during active arthritis increased disease severity. Conversely, bypassing the requirement for tryptophan degradation by the administration of L -kynurenine resulted in amelioration of arthritis. Furthermore, IDO-deficient mice showed a higher incidence of arthritis and exacerbated disease severity compared with IDO-competent mice. Such increased disease activity in IDO-deficient mice correlated early with increased production of the proinflammatory cytokines interferon-, and interleukin-17 by lymph node T cells and later with increased infiltration of Th1 and Th17 cells in the inflamed joints. Conclusion Our data indicate that the induction of IDO controls the accumulation of Th1 and Th17 pathogenic T cells at the site of inflammation during collagen-induced arthritis. Therefore, manipulation of the kynurenine pathway of tryptophan degradation provides the potential for therapeutic intervention in rheumatoid arthritis. [source]