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Secondary Lymphoid Tissues (secondary + lymphoid_tissue)

Distribution by Scientific Domains
Medical Sciences87%

Selected Abstracts

NK cells of human secondary lymphoid tissues enhance T cell polarization via IFN-, secretion

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2006
Barbara Morandi
Abstract Human secondary lymphoid tissues harbor NK cells that predominantly secrete cytokines in response to activation. Here, we demonstrate that these immunoregulatory NK cells assist in the Th1 polarization of primary immune responses, induced by dendritic cells. Tonsilar, but not peripheral blood NK cells enhanced the expansion of IFN-,-producing CD4+ T cells via their superior ability to produce IFN-,. Addition of IFN-, increased Th1 polarization while antibody blocking of this cytokine abolished NK cell-dependent Th1 polarization. Our data suggest that NK cells in secondary lymphoid organs assist priming of Th1 cells via cytokine secretion and this effect should be harnessed during vaccination against viruses and tumors. [source]

Lymphotoxin and LIGHT signaling pathways and target genes

IMMUNOLOGICAL REVIEWS, Issue 1 2004
Kirsten Schneider
Summary:, Lymphotoxins (LT, and LT,), LIGHT [homologous to LT, inducible expression, competes with herpes simplex virus (HSV) glycoprotein D for HSV entry mediator (HVEM), a receptor expressed on T lymphocytes], tumor necrosis factor (TNF), and their specific receptors LT,R, HVEM, and TNF receptor 1 (TNFR1) and TNFR2, form the immediate family of the larger TNF superfamily. These cytokines establish a critical communication system required for the development of secondary lymphoid tissues; however, knowledge of the target genes activated by these signaling pathways is limited. Target genes regulated by the LT,,-LT,R pathway include the tissue-organizing chemokines, CXCL13, CCL19, and CCL21, which establish cytokine circuits that regulate LT expression on lymphocytes, leading to organized lymphoid tissue. Infectious disease models have revealed that LT,, pathways are also important for innate and adaptive immune responses involved in host defense. Here, regulation of interferon-, by LT,R and TNFR signaling may play a crucial role in certain viral infections. Regulation of autoimmune regulator in the thymus via LT,R implicates LT/LIGHT involvement in central tolerance. Dysregulated expression of LIGHT overrides peripheral tolerance leading to T-cell-driven autoimmune disease. Blockade of TNF/LT/LIGHT pathways as an intervention in controlling autoimmune diseases is attractive, but such therapy may have risks. Thus, identifying and understanding the target genes may offer an opportunity to fine-tune inhibitory interventions. [source]

Chemokine receptor-dependent alloresponses

IMMUNOLOGICAL REVIEWS, Issue 1 2003
Wayne W. Hancock
Summary:, Immunologists have typically viewed alloreactivity schematically as a function of antigen presentation, expansion of alloreactive T and B cells within regional lymphoid tissues, and cellular infiltration and destruction of an allograft. Actual details of the steps between immune activation and accumulation of effector cells within a graft typically have not received much attention. However, just how cells ,know' to move to and migrate within a graft or not is proving to be of increasing interest, as the chemokine-dependent mechanisms underlying leukocyte recruitment to a transplant are dissected. Experimentally, chemokine receptor targeting can prolong or induce permanent allograft survival, despite preservation of alloresponses within secondary lymphoid tissues, whereas current immunosuppressive protocols have only modest effects on chemokine production and leukocyte homing. Recent knowledge of the chemokine-dependent nature of allograft rejection, acceptance, and tolerance induction are presented as a basis for understanding the rationale for preclinical trials of chemokine receptor-targeted therapies currently underway in primate recipients of solid organ allografts. [source]

CD56bright natural killer (NK) cells: an important NK cell subset

IMMUNOLOGY, Issue 4 2009
Aurélie Poli
Summary Human natural killer (NK) cells can be subdivided into different populations based on the relative expression of the surface markers CD16 and CD56. The two major subsets are CD56bright CD16dim/, and CD56dim CD16+, respectively. In this review, we will focus on the CD56bright NK cell subset. These cells are numerically in the minority in peripheral blood but constitute the majority of NK cells in secondary lymphoid tissues. They are abundant cytokine producers but are only weakly cytotoxic before activation. Recent data suggest that under certain conditions, they have immunoregulatory properties, and that they are probably immediate precursors of CD56dim NK cells. CD56bright NK cell percentages are expanded or reduced in a certain number of diseases, but the significance of these variations is not yet clear. [source]

Therapeutic effects of a new lymphocyte homing reagent FTY720 in interleukin-10 gene-deficient mice with colitis

INFLAMMATORY BOWEL DISEASES, Issue 3 2004
Tsunekazu Mizushima MD
Abstract Background: FTY720 is a novel reagent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY720 is mediated by completely different mechanisms from those of conventional immunosuppressants, that is, by altering the tissue distribution of lymphocytes rather than inhibiting activation. In this study, we examined the efficacy of FTY720 in the treatment of chronic colitis in an interleukin-10 gene-deficient (IL-10,/,) mouse model. Methods: FTY720 was administered orally for 4 weeks to IL-10,/,mice with clinical signs of colitis. The gross and histologic appearance of the colon and the numbers, phenotype, cytokine production, and apoptosis of lymphocytes were compared with those characteristics in a control group. Results: Single-dose administration of FTY720 resulted in the sequestration of circulating lymphocytes within the secondary lymphoid tissues. Four-week administration resulted in a significant reduction of the CD4+ T lymphocytes subpopulation in the colonic lamina propria and IFN-, production of the colonic lymphocytes, accompanied by a significant decrease in the severity of colitis. Conclusions: Treatment of established colitis in IL-10,/, mice with FTY720 ameliorated the colitis, probably as a result of decreasing the number of lymphocytes in the colonic mucosa and an associated reduction in IFN-, production. [source]

Dendritic cell vaccination and immune monitoring

ISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue 1 2009
E. H. J. G. Aarntzen
Dendritic cells (DCs) are the professional antigen-presenting cells of the immune system. Following infection or inflammation, they undergo a complex process of maturation and migrate to lymph nodes where they present antigens to T cells. Their decisive role in inducing immunity formed the rationale for DC immunotherapy: DCs loaded with tumour antigens are injected into cancer patients to stimulate T cells to eradicate tumours. Effective immune responses and favourable clinical outcomes have indeed been observed, but only in a minority of patients. Therefore, it is obvious that current DC-based protocols need to be improved. For this reason, we study in small proof-of-principle trials the fate, interactions and effectiveness of the injected DC. The success of DC-based immunotherapy to induce cellular immunity against tumours is highly dependent on accurate delivery and trafficking of the DC to T cell-rich areas of secondary lymphoid tissues. [source]

Whole-body autoradiography reveals that the Peptostreptococcus magnus immunoglobulin-binding domains of protein L preferentially target B lymphocytes in the spleen and lymph nodes in vivo

CELLULAR MICROBIOLOGY, Issue 7 2004
David Smith
Summary Protein L is an immunoglobulin (Ig)-binding protein produced by the Gram-positive bacterium Peptostreptococcus magnus that interacts with the variable region of Ig , light chains. The Ig light chain-binding capacity of protein L gives it the potential to interact with cells expressing surface Ig such as B cells. The present study was performed to address the in vivo trafficking of protein L at both the organ and the cellular level. Using the powerful technique of whole-body autoradiography in a murine model system, we demonstrate specific targeting of protein L to secondary lymphoid tissues in whole-animal analysis. The observed targeting depends on the capacity to interact with murine Ig, as tissue targeting was not apparent in mice given protein H, an Ig-binding protein produced by Streptococcus pyogenes with affinity for human but not murine Ig. Tissue targeting data were combined with flow cytometry analysis, which demonstrated the capacity of protein L to target and activate B lymphocytes in vivo. B cells targeted by protein L had increased surface expression of CD86 and MHC-II, and protein L was present in vacuolar compartments of B cells. Protein L did not bind T cells or natural killer cells but had some capacity to target dendritic cells and macrophages. The data show that protein L preferentially targets secondary lymphoid organs, and activates and is internalized by B cells in vivo. Furthermore, the observed tissue and cell targeting properties require an affinity for murine Ig. These data support the potential use of this Ig-binding protein as a targeting approach to deliver agents to defined cell populations in vivo. [source]