Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization

Gunn, Michael D.; Kyuwa, Shigeru; Tam, Carmen; Kakiuchi, Terutaka; Matsubara, Akio; Williams, Lewis T.; Nakano, Hideki

doi:10.1084/jem.189.3.451

Cited by 936 publications

(876 citation statements)

References 55 publications

(65 reference statements)

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“…In contrast, antigen encounter by naïve CD4 cells on B cells results in the induction of tolerance [29]. In vivo, a highly developed lymphoid architecture along with defined migration pathways ascertain the encounter of naïve CD4 cells with the proper APC [30][31][32]. For CD8 cells, chemokines have recently been shown to play a critical role in attracting the few antigen-specific naïve cells to the site of DC-CD4 cell interaction in lymph nodes [33].…”

Section: Discussionmentioning

confidence: 99%

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

Ott¹,

Tary‐Lehmann²,

Lehmann³

2007

Clinical Immunology

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It is unknown to what extent the heterogeneity of antigen presenting cells (APC) influences the IFN-γ response of CD4 memory cells. We restimulated DO11.10 T cell receptor (TCR)-transgenic cells and wild-type CD4 memory cells with OVA-peptide 323 -339 presented on purified dendritic cells (DC), macrophages, and B cells. Using IFN-γ ELISPOT assays we measured the number of cytokine producing T cells and the amount of cytokine produced by individual T cells at different time points after antigen encounter. The data showed that, when CD4 cells recognized antigen on DC, the induction of cytokine production was accelerated compared to macrophages and B cells. In contrast, the per-cell cytokine productivity was independent of the type of APC by which the T cells were restimulated. Moreover, the peptide concentration required for CD4 cell activation was comparable for the different APC. The data suggest that DC induce cytokine production in memory cells with accelerated activation kinetics, whereas 24 h of antigen stimulation on DC, macrophages, and B cells results in comparable levels of T cell activation. These data have implications for the understanding of T cell memory responses when T cells re-encounter antigen on different APC as well as for the monitoring of memory T cell responses ex vivo.

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Section: Discussionmentioning

confidence: 99%

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

Ott¹,

Tary‐Lehmann²,

Lehmann³

2007

Clinical Immunology

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“…[26][27][28] One of the best candidates for chemokines is CCL21, which has been proposed to play a role in favoring the interactions between DCs and T cells in secondary lymphoid organs through CCR7 receptor. 4,7,9,29 In fact, mice deficient in the expression of CCL21 showed defects in lymphocyte homing and DC localization, 30 and mice lacking CCR7 receptor also had defects in lymph node architecture. 31 Furthermore, it has been demonstrated that CCL21 could participate itself in lymphoid tissue development and organization in a transgenic model where the CCL21 gene was expressed in pancreatic islets.…”

Section: Discussionmentioning

confidence: 99%

Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT

et al. 2004

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To establish a more efficient treatment for immunotherapy against solid tumors, we have evaluated the antitumor effect by coexpression of a chemokine CCL21/secondary lymphoid tissue chemokine and a costimulatory molecule LIGHT in colon carcinoma C26. C26 cells expressing either CCL21 or LIGHT exhibited a significantly reduced tumor growth in vivo, and mice inoculated with these cells showed a prolonged survival, but eventually all these mice died. In contrast, C26 cells expressing both CCL21 and LIGHT exhibited a minimal tumor growth in vivo, and all these mice survived healthily with a tumor remission and consequently acquired a strong protective immunity. A markedly increased infiltration of mature dendritic cells (DCs), and CD8 þ T cells was observed in the tumor mass, and their spleen cells showed a greatly enhanced cytotoxic T lymphocyte (CTL) activity against C26 tumor and interferon (IFN)-g production. Neutralization of IFN-g or depletion of CD8 þ or CD4 þ T cells significantly reduced the antitumor activity. These results suggest that the combined treatment with CCL21 and LIGHT is able to induce a synergistic antitumor effect to eradicate tumor completely by greatly enhancing tumor-infiltration of lymphocytes including mature DCs and CD8 þ T cells, resulting in markedly augmented CTL activity and IFN-g production.

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“…Surprisingly, observations made J. Cyster and collaborators discovered that intrinsic LTβR signaling in hematopoietic cells provided trophic signals necessary for the proliferation CD8α− DC subsets in spleen and lymph node, independent of chemokine expression [18,19]. Moreover, the number of DC in plt (paucity of lymph node T cells) mice, lacking both CCL19 and CCL21 chemokines, was comparable to wild-type mice and required LTβR signaling [20]. The lack of TNF, which also decreases the expression of CXCL13, does not alter DC subsets in vivo, but participates in DC generation from bone marrow precursor cells in GM-CSF cultures suggesting the role played by TNF is redundant in vivo [16].…”

Section: Nih Public Accessmentioning

confidence: 99%

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

Trez

Ware

2008

Cytokine & Growth Factor Reviews

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Dendritic cells (DC) constitute the most potent antigen presenting cells of the immune system, playing a key role bridging innate and adaptive immune responses. Specialized DC subsets differ depending on their origin, tissue location and the influence of trophic factors, the latter remain to be fully understood. Stromal cell and myeloid-associated Lymphotoxin-β receptor (LTβR) signaling is required for the local proliferation of lymphoid tissue DC. This review focuses the LTβR signaling cascade as a crucial positive trophic signal in the homeostasis of DC subsets. The noncanonical coreceptor pathway comprised of the Immunoglobulin (Ig) superfamily member, B and T lymphocyte attenuator (BTLA) and TNFR superfamily member, Herpesvirus entry mediator (HVEM) counter regulates the trophic signaling by LTβR. Together both pathways form an integrated signaling circuit achieving homeostasis of DC subsets.Keywords dendritic cells; homeostasis; TNF superfamily; cosignaling; lymphotoxin; herpesvirus entry mediator Dendritic CellsDendritic cells (DC) originate from hematopoietic precursors and can be divided in several subsets depending on their anatomical location, surface phenotype and function. For example, two broad classes of DC are the peripheral migratory DC and the lymphoid tissue-resident DC [1]. The migratory DC, i.e. the dermal DC and Langerhans cells, can be considered as sentinels of the immune system as they form a sensing barrier in peripheral tissues at the interface with environment. The lymphoid tissue-resident DC include the splenic and thymic DC.Dendritic cells are specialized in the capture, transport, processing and presentation of antigens. In the presence of a microbial stimulus, these steps are associated with further DC differentiation (maturation) characterized by upregulation of costimulatory and major histocompatibility complex (MHC) molecules. As DC become activated they migrate to or Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Both spleen and lymph node lymphoid tissue-resident DC possess a half-life of about three days. Despite their rapid turnover, little is known about the factors controlling immediate precursors and homeostasis in vivo. In earlier studies, CD8α expression was used to distinguish between "lymphoid" and "myeloid" DC. However, more recent experiments showed that different DC subsets could differentiate from both lymphoid and myeloid precursors [6,7]. CD8α marker remains very useful to discriminate between subsets, but no longer defines a subset origin. Recently, the group of Shortman provided in vivo and in vitro evidence fo...

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Mice Lacking Expression of Secondary Lymphoid Organ Chemokine Have Defects in Lymphocyte Homing and Dendritic Cell Localization

Cited by 936 publications

References 55 publications

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

The secretory IFN-γ response of single CD4 memory cells after activation on different antigen presenting cell types

Synergistic antitumor effect by coexpression of chemokine CCL21/SLC and costimulatory molecule LIGHT

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

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