scholarly journals Cooperating Mechanisms of CXCR5 and CCR7 in Development and Organization of Secondary Lymphoid Organs

2003 ◽  
Vol 197 (9) ◽  
pp. 1199-1204 ◽  
Author(s):  
Lars Ohl ◽  
Golo Henning ◽  
Stefan Krautwald ◽  
Martin Lipp ◽  
Svenja Hardtke ◽  
...  
Keyword(s):  
Functional Organization ◽  
Mesenchymal Cells ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
White Pulp ◽  
Organ Development ◽  
Secondary Lymphoid Organ ◽  
Small Clusters ◽  
Secondary Lymphoid Organs ◽  
Deficient Mice

Homeostatic chemokines participate in the development of secondary lymphoid organs and later on in the functional organization of these tissues. The development of lymph nodes (LNs) and Peyer's patches depends on the recruitment of CD3− CD4+ interleukin (IL)-7Rαhi cells to sites of future organ development. CD3− CD4+ IL-7Rαhi cells express the chemokine receptor CXCR5 and might be attracted by its ligand CXCL13, which is secreted by mesenchymal cells. Mesenchymal cells also secrete CCL19, a ligand for CCR7, yet it is not clear whether CCR7 and CCL19 are important for secondary lymphoid organ development. Analyzing CXCR5−/− CCR7−/− double deficient mice we now show that these mice lack all examined peripheral LNs suggesting a profound role for both receptors in secondary lymphoid organ development. We demonstrate that CD3− CD4+ IL-7Rαhi cells express CXCR5 as well as CCR7 indicating that both receptors cooperate during an early step of secondary lymphoid organ development. Furthermore, CXCR5−/− CCR7−/− mice display a severely disturbed architecture of mesenteric LN and spleen. Due to an impaired migration of B cells into the white pulp, CXCR5−/− CCR7−/− mice fail to develop B cell follicles but show small clusters of unorganized lymphocytes in the spleen. These data demonstrate a cooperative function of CXCR5 and CCR7 in lymphoid organ organogenesis and organization.

scholarly journals Plasma cell S1P1 expression determines secondary lymphoid organ retention versus bone marrow tropism

2006 ◽  
Vol 203 (12) ◽  
pp. 2683-2690 ◽  
Author(s):  
Kenji Kabashima ◽  
Nicole M. Haynes ◽  
Ying Xu ◽  
Stephen L. Nutt ◽  
Maria L. Allende ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Secondary Response ◽  
Secondary Lymphoid Organ ◽  
Lower Blood ◽  
Sphingosine 1 Phosphate ◽  
Secondary Lymphoid Organs

After induction in secondary lymphoid organs, a subset of antibody-secreting cells (ASCs) homes to the bone marrow (BM) and contributes to long-term antibody production. The factors determining secondary lymphoid organ residence versus BM tropism have been unclear. Here we demonstrate that in mice treated with FTY720 or that lack sphingosine-1-phosphate (S1P) receptor-1 (S1P1) in B cells, IgG ASCs are induced and localize normally in secondary lymphoid organs but they are reduced in numbers in blood and BM. Many IgG ASCs home to BM on day 3 of the secondary response and day 3 splenic ASCs exhibit S1P responsiveness, whereas the cells remaining at day 5 are unable to respond. S1P1 mRNA abundance is higher in ASCs isolated from blood compared to spleen, whereas CXCR4 expression is lower. Blood ASCs also express higher amounts of Kruppel-like factor (KLF)2, a regulator of S1P1 gene expression. These findings establish an essential role for S1P1 in IgG plasma cell homing and they suggest that differential regulation of S1P1 expression in differentiating plasma cells may determine whether they remain in secondary lymphoid organs or home to BM.

scholarly journals Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit

2005 ◽  
Vol 201 (2) ◽  
pp. 291-301 ◽  
Author(s):  
Charles G. Lo ◽  
Ying Xu ◽  
Richard L. Proia ◽  
Jason G. Cyster
Keyword(s):  
Lymph Nodes ◽  
Surface Expression ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
White Pulp ◽  
Activated T Cells ◽  
Circulating Lymphocytes ◽  
Sphingosine 1 Phosphate ◽  
Splenic White Pulp ◽  
Lymphocyte Egress

Sphingosine-1-phosphate receptor 1 (S1P1) was recently shown to be required for lymphocyte egress from lymphoid organs. Here we have examined the relationship between S1P1 abundance on the cell and egress efficiency. Using an integrin neutralization approach to separate the processes of entry and exit, we show that pertussis toxin treatment reduces lymphocyte egress from lymph nodes. Retrovirally mediated S1P1 overexpression is sufficient to reduce B cell accumulation in the splenic white pulp and to promote egress of activated T cells from lymph nodes, whereas S1P1+/−cells have reduced lymph node exit efficiency. Furthermore, lymphocyte S1P1 is down-regulated in the blood, up-regulated in lymphoid organs, and down-regulated again in the lymph. We propose that cyclical ligand-induced modulation of S1P1 on circulating lymphocytes contributes to establishing their lymphoid organ transit time.

scholarly journals Similar antigen cross-presentation capacity and phagocytic functions in all freshly isolated human lymphoid organ–resident dendritic cells

2013 ◽  
Vol 210 (5) ◽  
pp. 1035-1047 ◽  
Author(s):  
Elodie Segura ◽  
Mélanie Durand ◽  
Sebastian Amigorena
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Endocytic Pathway ◽  
Soluble Antigen ◽  
Cross Presentation ◽  
Antigen Presenting ◽  
Secondary Lymphoid Organs

Dendritic cells (DCs) represent a heterogeneous population of antigen-presenting cells that initiate and orient immune responses in secondary lymphoid organs. In mice, lymphoid organ–resident CD8+ DCs are specialized at cross-presentation and have developed specific adaptations of their endocytic pathway (high pH, low degradation, and high export to the cytosol). In humans, blood BDCA3+ DCs were recently shown to be the homologues of mouse CD8+ DCs. They were also proposed to cross-present antigens more efficiently than other blood DC subsets after in vitro activation, suggesting that in humans cross-presentation is restricted to certain DC subsets. The DCs that cross-present antigen physiologically, however, are the ones present in lymphoid organs. Here, we show that freshly isolated tonsil-resident BDCA1+ DCs, BDCA3+ DCs, and pDCs all cross-present soluble antigen efficiently, as compared to macrophages, in the absence of activation. In addition, BDCA1+ and BDCA3+ DCs display similar phagosomal pH and similar production of reactive oxygen species in their phagosomes. All three DC subsets, in contrast to macrophages, also efficiently export internalized proteins to the cytosol. We conclude that all freshly isolated lymphoid organ–resident human DCs, but not macrophages, display high intrinsic cross-presentation capacity.

The Lymphoid Chemokine CCL21 Enhances the Migration- and CTL-Inducing Functions of Dendritic Cells

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1127-1127
Author(s):  
Cheol Yi Hong ◽  
Pawel Kalinski ◽  
Hyeoung-Joon Kim ◽  
Je-Jung Lee
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Cd8 T Cells ◽  
Conflicts Of Interest ◽  
Cytotoxic T Cells ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Dependent Manner ◽  
Migratory Capacity ◽  
Secondary Lymphoid Organs

Abstract Abstract 1127 The migration of dendritic cells (DCs) to secondary lymphoid organs is very important to elicit an adaptive immune response in cancer immunotherapy. Here, we show the effect of lymphoid cytokine on the ability of maturing DCs to migrate in response to the lymph node-associated chemokines. The secondary-lymphoid organ chemokine (SLC/CCL21) during DC maturation dramatically enhanced DC migratory capacity responding to CCL21 and CCL19, and, moreover, produced strongly enhanced cytotoxic T cells, although it did not affect the expression of cell surface markers such as CD80, CD83, CD86, and CCR7 and the production of cytokines such as IL-12p70, IL-10, and IL-23. Mature DCs (mDCs) exposed by chemokine produced higher levels of CXCL10 (IP-10) that is one of the chemokines involved in Th1 attraction, but did not affect the production of Th2-attracting cytokine CCL22, compared with unstimulated mDCs. CCL21-exposed DCs induced strongly enhanced numbers of the interferon-g (IFN-g)-expressing antigen-specific CD8+ T cells against tumor-specific antigens in an CXCL10-dependent manner. Cytotoxic CD8+ T cells stimulated with CCL21-exposed DCs expressed higher level of IFN-g than those stimulated with control mDCs. Interestingly, generation of cytotoxic T cells (CTLs) stimulated by TNFa/IL-1b/IL-6/PGE2-treated DCs (sDCs) supplemented with IP-10 produced strong cytotoxic T cells expressing higher level of IFN-g. Tetramer assay showed that CCL21-treated DCs enhanced generation of antigen-specific CTLs. Taken together, our data suggest that mDCs pre-stimulated by chemokine CCL21 enhanced migratory capacity to secondary lymphoid organs and produced strong cytotoxic T cells via IP-10 signaling pathway. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Deletion of DOCK2, a regulator of the actin cytoskeleton in lymphocytes, suppresses cardiac allograft rejection

2005 ◽  
Vol 202 (8) ◽  
pp. 1121-1130 ◽  
Author(s):  
Hongsi Jiang ◽  
Fan Pan ◽  
Laurie M. Erickson ◽  
Mei-Shiang Jang ◽  
Terukazu Sanui ◽  
...  
Keyword(s):  
T Cells ◽  
Actin Cytoskeleton ◽  
Allograft Rejection ◽  
Critical Role ◽  
Lymphoid Organs ◽  
Term Survival ◽  
Alloreactive T Cells ◽  
Secondary Lymphoid Organs ◽  
Deficient Mice

Allograft rejection is induced by graft tissue infiltration of alloreactive T cells that are activated mainly in secondary lymphoid organs of the host. DOCK2 plays a critical role in lymphocyte homing and immunological synapse formation by regulating the actin cytoskeleton, yet its role in the in vivo immune response remains unknown. We show here that DOCK2 deficiency enables long-term survival of cardiac allografts across a complete mismatch of the major histocompatibility complex molecules. In DOCK2-deficient mice, alloreactivity and allocytotoxicity were suppressed significantly even after in vivo priming with alloantigens, which resulted in reduced intragraft expression of effector molecules, such as interferon-γ, granzyme B, and perforin. This is mediated, at least in part, by preventing potentially alloreactive T cells from recruiting into secondary lymphoid organs. In addition, we found that DOCK2 is critical for CD28-mediated Rac activation and is required for the full activation of alloreactive T cells. Although DOCK2-deficient, alloreactive T cells were activated in vitro in the presence of exogenous interleukin-2, these T cells, when transferred adoptively, failed to infiltrate into the allografts that were transplanted into RAG1-deficient mice. Thus, DOCK2 deficiency attenuates allograft rejection by simultaneously suppressing multiple and key processes. We propose that DOCK2 could be a novel molecular target for controlling transplant rejection.

scholarly journals Incidence of Apoptosis in the Lymphoid Organs of Normal or Malaria Infected Mice is Decreased in CD18 and Urokinase - Receptor (UPAR, CD87) Deficient Mice

2001 ◽  
Vol 8 (3-4) ◽  
pp. 183-191 ◽  
Author(s):  
Pierre Francois Piguet ◽  
Chen da Laperrousaz ◽  
Christian Vesin ◽  
Yves Donati
Keyword(s):  
Lymph Nodes ◽  
Annexin V ◽  
Urokinase Receptor ◽  
Lymphoid Organs ◽  
White Pulp ◽  
Facs Analysis ◽  
Surface Molecules ◽  
Spleen And Lymph Nodes ◽  
Serum Igg Levels ◽  
Deficient Mice

Incidence of apoptosis was investigated in the spleen and lymph nodes of +/+, CD18 -/- and urokinase receptor (uPAR, CD87) -/- mice, untreated orPlasmodium Berghei Anka(PbA) infected. In non infected mice, incidence of apoptosis was lower in the lymph nodes of CD18 -/- and uPAR -/- than in +/+ mice, as seen by FACS analysis to count the number of hypodiploid and Annexin-V binding cells. Infection of mice with PbA resulted in a marked increase in the size of spleen and lymph nodes 7–8 days after infection, which was slightly higher in uPAR -/- and CD18 -/- than in +/+ mice. PbA infection increased about 7 fold the incidence of apoptosis in the lymphoid organs of +/+, especially in the white pulp and germinal centers of the spleen and lymph nodes, while in contrast it was unchanged in PbA infected CD18 -/- or uPAR -/- mice. Serum IgG levels, and number of circulating leukocytes were significantly higher in both uPAR and CD18 -/- than in +/+ mice. These results indicate that the CD18 and uPAR surface molecules, which are known to be associated in the cell membrane, have an important influence upon the incidence of cell survival in both normal or stimulated lymphoid organs.

scholarly journals Cellular source and molecular form of TNF specify its distinct functions in organization of secondary lymphoid organs

Blood ◽  
2010 ◽  
Vol 116 (18) ◽  
pp. 3456-3464 ◽  
Author(s):  
Alexei V. Tumanov ◽  
Sergei I. Grivennikov ◽  
Andrei A. Kruglov ◽  
Yuriy V. Shebzukhov ◽  
Ekaterina P. Koroleva ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
Molecular Form ◽  
Lymphoid Organ ◽  
Lymphoid Organs ◽  
Conditional Knockout ◽  
Cellular Source ◽  
Membrane Bound ◽  
Secondary Lymphoid Organs

Abstract Secondary lymphoid organs provide a unique microenvironment for generation of immune responses. Using a cell type–specific conditional knockout approach, we have dissected contributions of tumor necrosis factor (TNF) produced by B cells (B-TNF) or T cells (T-TNF) to the genesis and homeostatic organization of secondary lymphoid organs. In spleen, lymph nodes and Peyer patches, the cellular source of TNF, and its molecular form (soluble versus membrane-bound) appeared distinct. In spleen, in addition to major B-TNF signal, a complementary T-TNF signal contributed to the microstructure. In contrast, B-TNF predominantly controlled the development of follicular dendritic cells and B-cell follicles in Peyer patches. In lymph nodes, cooperation between TNF expressed by B and T cells was necessary for the maintenance of microarchitecture and for generation of an efficient humoral immune response. Unexpectedly, soluble but not membrane TNF expressed by B cells was essential for the organization of the secondary lymphoid organs. Thus, the maintenance of each type of secondary lymphoid organ is orchestrated by distinct contributions of membrane-bound and soluble TNF produced by B and T lymphocytes.

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