scholarly journals The chemokine SLC is expressed in T cell areas of lymph nodes and mucosal lymphoid tissues and attracts activated T cells via CCR7

1998 ◽  
Vol 28 (6) ◽  
pp. 2025-2034 ◽  
Author(s):  
Katharina Willimann ◽  
Daniel F. Legler ◽  
Marcel Loetscher ◽  
Regula Stuber Roos ◽  
Maria Belen Delgado ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Lymphoid Tissues ◽  
Activated T Cells

scholarly journals In situ immunologic characterization of cellular constituents in lymph nodes and spleens involved by Hodgkin's disease

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 226-232 ◽  
Author(s):  
S Poppema ◽  
AK Bhan ◽  
EL Reinherz ◽  
MR Posner ◽  
SF Schlossman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cytotoxic T Cells ◽  
Lymphoid Tissues ◽  
Immunoperoxidase Technique ◽  
Activated T Cells ◽  
Cytoplasmic Staining

The cellular constituents in lymph nodes and spleens of patients with Hodgkin's disease were studied with a series of monoclonal antibodies directed against human thymocyte, peripheral T-cell, and la antigens. Utilizing both an immunoperoxidase technique on frozen tissue sections and indirect immunofluorescence on cell suspensions, wer found that a majority of lymphocytes were T cells, since they stained with anti-T1 and anti-T3 antibodies, which react with all peripheral T cells. In addition, most of these cells were reactive with anti-T4 antibody, which defines the helper/inducer T-cell population, whereas only a minority of cells stained with anti-T5 and anti-T8 antibodies, which are reactive with suppressor/cytotoxic T cells. Moreover, a large proportion of T cells expressed T10 antigen, which is found on activated T cells. A minority of the T cells also expressed la antigen(s), again suggesting that some of the T cells are activated. In contrast, the Reed-sternberg cells did not react with any of these anti- T-cell antibodies or with anti-IgM antiserum, but displayed strong membrane and cytoplasmic staining with anti-la antibody. Taken together, these findings suggest that Reed-Sternberg cells are not of T- cell lineage but may be derived from antigen-presenting reticulum cells in the thymus-dependent areas of lymphoid tissues; these cells are normally associated with T4+ cells.

scholarly journals In situ immunologic characterization of cellular constituents in lymph nodes and spleens involved by Hodgkin's disease

Blood ◽  
1982 ◽  
Vol 59 (2) ◽  
pp. 226-232 ◽  
Author(s):  
S Poppema ◽  
AK Bhan ◽  
EL Reinherz ◽  
MR Posner ◽  
SF Schlossman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Cytotoxic T Cells ◽  
Lymphoid Tissues ◽  
Immunoperoxidase Technique ◽  
Activated T Cells ◽  
Cytoplasmic Staining

Abstract The cellular constituents in lymph nodes and spleens of patients with Hodgkin's disease were studied with a series of monoclonal antibodies directed against human thymocyte, peripheral T-cell, and la antigens. Utilizing both an immunoperoxidase technique on frozen tissue sections and indirect immunofluorescence on cell suspensions, wer found that a majority of lymphocytes were T cells, since they stained with anti-T1 and anti-T3 antibodies, which react with all peripheral T cells. In addition, most of these cells were reactive with anti-T4 antibody, which defines the helper/inducer T-cell population, whereas only a minority of cells stained with anti-T5 and anti-T8 antibodies, which are reactive with suppressor/cytotoxic T cells. Moreover, a large proportion of T cells expressed T10 antigen, which is found on activated T cells. A minority of the T cells also expressed la antigen(s), again suggesting that some of the T cells are activated. In contrast, the Reed-sternberg cells did not react with any of these anti- T-cell antibodies or with anti-IgM antiserum, but displayed strong membrane and cytoplasmic staining with anti-la antibody. Taken together, these findings suggest that Reed-Sternberg cells are not of T- cell lineage but may be derived from antigen-presenting reticulum cells in the thymus-dependent areas of lymphoid tissues; these cells are normally associated with T4+ cells.

CD4+ T cells are essential for the development of destructive thyroiditis induced by anti–PD-1 antibody in thyroglobulin-immunized mice

2021 ◽  
Vol 13 (593) ◽  
pp. eabb7495
Author(s):  
Yoshinori Yasuda ◽  
Shintaro Iwama ◽  
Daisuke Sugiyama ◽  
Takayuki Okuji ◽  
Tomoko Kobayashi ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Mononuclear Cells ◽  
Critical Role ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Histopathological Analysis ◽  
Activated T Cells ◽  
Cervical Lymph Nodes

Immune-related adverse events induced by anti–programmed cell death–1 antibodies (PD-1-Ab), including destructive thyroiditis (thyroid-irAE), are thought to be caused by activated T cells. However, the T cell subsets that are directly responsible for damaging self-organs remain unclear. To clarify which T cell subsets are involved in the development of thyroid-irAE, a mouse model of thyroid-irAE was analyzed. PD-1-Ab administration 2.5 months after immunization with thyroglobulin caused destructive thyroiditis. Thyroiditis was completely prevented by previous depletion of CD4+ T cells and partially prevented by depleting CD8+ T cells. The frequencies of central and effector memory CD4+ T cell subsets and the secretion of interferon-γ after stimulation with thyroglobulin were increased in the cervical lymph nodes of mice with thyroid-irAE compared with controls. Histopathological analysis revealed infiltration of CD4+ T cells expressing granzyme B in thyroid glands and major histocompatibility complex class II expression on thyrocytes in mice with thyroid-irAE. Adoptive transfer of CD4+ T cells from cervical lymph nodes in mice with thyroid-irAE caused destruction of thyroid follicular architecture in the irradiated recipient mice. Flow cytometric analyses showed that the frequencies of central and effector memory CD4+ T cells expressing the cytotoxic marker CD27 were higher in peripheral blood mononuclear cells collected from patients with thyroid-irAE induced by PD-1-Ab versus those without. These data suggest a critical role for cytotoxic memory CD4+ T cells activated by PD-1-Ab in the pathogenesis of thyroid-irAE.

scholarly journals The Effect of Antigen Stimulation on the Migration of Mature T Cells from the Peripheral Lymphoid Tissues to the Thymus

2001 ◽  
Vol 8 (2) ◽  
pp. 123-131 ◽  
Author(s):  
Charles L. Hardy ◽  
Dale I. Godfrey ◽  
Roland Scollay
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymphoid Tissue ◽  
Lymphoid Tissues ◽  
Activated T Cells ◽  
Cell Pool ◽  
Peripheral Lymphoid Tissue ◽  
Cognate Antigen ◽  
Transgenic Cells ◽  
Peripheral Cells

Although the maturation and export of T cells from the thymus has been extensively studied, the movement of cells in the opposite direction has been less well documented. In particular, the question of whether T cells which have been activated by antigen in the periphery are more likely to return to the thymus had been raised but not clearly answered. We examined this issue by activating T cells present in the periphery with their cognate antigen, and assessing migration to the thymus. TCR-transgenic cells from OT-I mice (Thy1.2+), which recognise the ovalbumin peptide OVA257–264in the context of H-2Kb, were transferred into otherwise unmanipulated Thy1.1+C57BL/6 mice. Recipient mice were injected i.v. with 5μgpeptide (SIINFEKL) approximately 24 hours later. The numbers of donor-derived (Thy1.2+) cells in the thymus and peripheral lymphoid tissue were determined. The results clearly show increased numbers of transgenic cells in the thymus 3 days after antigenic stimulation. However, since numbers of transgenic cells increased in the spleen and LN in about the same proportion, the data do not support the notion that there is highly increased selective migration of activated T cells to the thymus. Rather, they suggest that a sample of peripheral cells enters the thymus each day, and that the mature immigrants detected in the thymus merely reflect the contents of the peripheral T cell pool.

scholarly journals Initiation of Autoimmune Diabetes by Developmentally Regulated Presentation of Islet Cell Antigens in the Pancreatic Lymph Nodes

1999 ◽  
Vol 189 (2) ◽  
pp. 331-339 ◽  
Author(s):  
Petter Höglund ◽  
Justine Mintern ◽  
Caroline Waltzinger ◽  
William Heath ◽  
Christophe Benoist ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Beta Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Molecular Mimicry ◽  
Autoimmune Diabetes ◽  
Activated T Cells ◽  
Pancreatic Lymph Nodes

Little is known about the events triggering lymphocyte invasion of the pancreatic islets in prelude to autoimmune diabetes. For example, where islet-reactive T cells first encounter antigen has not been identified. We addressed this issue using BDC2.5 T cell receptor transgenic mice, which express a receptor recognizing a natural islet beta cell antigen. In BDC2.5 animals, activated T cells were found only in the islets and the lymph nodes draining them, and there was a close temporal correlation between lymph node T cell activation and islet infiltration. When naive BDC2.5 T cells were transferred into nontransgenic recipients, proliferating cells were observed only in pancreatic lymph nodes, and this occurred significantly before insulitis was detectable. Surprisingly, proliferation was not seen in 10-day-old recipients. This age-dependent dichotomy was reproduced in a second transfer system based on an unrelated antigen artificially expressed on beta cells. We conclude that beta cell antigens are transported specifically to pancreatic lymph nodes, where they trigger reactive T cells to invade the islets. Systemic or extrapancreatic T cell priming, indicative of activation via molecular mimicry or superantigens, was not seen. Compromised presentation of beta cell antigens in the pancreatic lymph nodes of juvenile animals may be the root of a first “checkpoint” in diabetes progression.

scholarly journals Pulmonary Interleukin-23 Gene Delivery Increases Local T-Cell Immunity and Controls Growth of Mycobacterium tuberculosis in the Lungs

2005 ◽  
Vol 73 (9) ◽  
pp. 5782-5788 ◽  
Author(s):  
Kyle I. Happel ◽  
Euan A. Lockhart ◽  
Carol M. Mason ◽  
Elizabeth Porretta ◽  
Elizabeth Keoshkerian ◽  
...  
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Gene Delivery ◽  
Lymph Nodes ◽  
T Cell Immunity ◽  
Activated T Cells ◽  
Cell Immunity ◽  
Ifn Γ ◽  
Interleukin 23

ABSTRACT Interleukin-23 (IL-23) is a heterodimeric cytokine that shares IL-12 p40 but contains a unique p19 subunit similar to IL-12 p35. Previous studies indicate a greater importance for intact IL-12/23 p40 expression than IL-12 p35 for immunity against Mycobacterium tuberculosis, suggesting a role for IL-23 in host defense. The effects of IL-23 on the outcome of pulmonary infection with M. tuberculosis have not been described. Here, we show that local delivery of replication-defective adenovirus vectors encoding IL-23 (AdIL-23) greatly stimulated expression of both gamma interferon (IFN-γ) and IL-17 in lung tissues of otherwise normal mice. When given 72 h prior to infection with M. tuberculosis, AdIL-23 significantly reduced the bacterial burden at 14, 21, and 28 days. Markedly lower levels of lung inflammation were observed at 28 days than in control mice pretreated with control adenovirus (AdNull) or vehicle controls. AdIL-23 pretreatment resulted in increased numbers of CD4+ CD25+ activated T cells in lungs and draining lymph nodes compared to control groups and more CD4+ T cells bearing surface memory markers in lung lymph nodes. IL-23 gene delivery also significantly enhanced host anti-mycobacterial T-cell responses, as shown by elevated levels of IFN-γ and IL-17 secreted in vitro following restimulation with M. tuberculosis purified protein derivative. Overall, our data show that transient IL-23 gene delivery in the lung is well tolerated, and they provide the initial demonstration that this factor controls mycobacterial growth while augmenting early pulmonary T-cell immunity.

scholarly journals T cells Mediate Progression of Load-Induced Osteoarthritis

2020 ◽  
Author(s):  
Tibra A. Wheeler ◽  
Adrien Y. Antoinette ◽  
Matthew J. Kim ◽  
Marjolein C. H. van der Meulen ◽  
Ankur Singh
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Lymph Nodes ◽  
Mechanical Loading ◽  
Joint Damage ◽  
Γδ T Cells ◽  
Cartilage Degradation ◽  
T Cell Response ◽  
Lymphoid Tissues

AbstractOsteoarthritis (OA) is a degenerative disease that manifests as joint damage and synovial inflammation. To date, most studies have focused on the decrease in cartilage stiffness, chondrocyte viability, and changes in matrix-degrading enzymes. With the exception of a few inflammatory cytokines and macrophages, the immune response in OA is poorly characterized, and the crosstalk of joint damage with T and B cells in local lymph nodes is unknown. Here, using an in vivo mouse model of mechanical loading of mouse tibia, we demonstrate that CD8+ T cells and subsets of CD4+ T cells, and not B cells, increase in the local lymph nodes and contribute to the progression of load-induced OA pathology. We demonstrate that T cell response is sex- and age-dependent. Mechanical loading of T cell knock-out mice that lack αβ T cell receptor carrying cells resulted in attenuation of both cartilage degradation and osteophyte formation in loaded joints, with a concomitant increase in γδ+ T cells. Restricting the migration of T cells in lymphoid tissues through the systemic treatment using Sphingosine-1-phosphate (S1P) inhibitor, decreased localization of T cells in synovium, and attenuated cartilage degradation. Our results lay the foundation of the role T cells play in the joint damage of load-induced OA and allude to the use of S1P inhibitors and T cell immunotherapies for slowing the progression of OA pathology.

Analysis Of T Cell Receptor Repertoire Reveals Evidence For Antigen-Specific Response In CLL Lymph Nodes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4141-4141
Author(s):  
Marta Pasikowska ◽  
Deborah Yallop ◽  
William M Townsend ◽  
Winston Vetharoy ◽  
Kirsty M Cuthill ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Cd4 T Cells ◽  
Cell Receptor ◽  
Cd4 Cells ◽  
Antigen Specificity ◽  
Activated T Cells ◽  
Tfh Cells ◽  
Tcr Diversity

Abstract It is now widely accepted that in chronic lymphocytic leukaemia (CLL), proliferation of the malignant B cell clone takes place in pseudofollicles positioned within lymphoid tissue. This complex environment is believed to provide CLL cells with signals necessary for survival and expansion. In recent years the role for T cells in these processes has started to emerge. By analysing formalin fixed paraffin embedded (FFPE) CLL lymph node (LN) sections by multi-parameter confocal microscopy, our group previously demonstrated that dividing CLL cells stay in close contact with CD4+ CD25+ Foxp3- T cells. In addition, in an in vitro assay, activated T cells were found to be capable of inducing CLL cell proliferation. Our subsequent flow cytometry analyses looked at the phenotype of the T cells isolated from the CLL lymph nodes by fine needle aspiration (FNA). LN T cells were found to express effector memory cell markers more commonly than their PB counterparts and also had much higher levels of the activation/exhaustion marker PD1. Since PD1 is known to be a marker of T follicular helper cells (Tfh), in our current work we asked if Tfh cells are a significant component of the T cell infiltrate of CLL lymph nodes. We used confocal immunofluorescent microscopy on FFPE CLL LN sections and looked for coexpression of CD4, PD1 and ICOS – also used to identify Tfh cells. PD1 was expressed on 25% of CD4+ cells (95% CI 21-30) but only 4% of CD4+ cells expressed both PD1 and ICOS (95% CI 2.5-5.6) (n=6). The number of Tfh cells infiltrating CLL LN was shown to be low when compared with the numbers found in normal reactive LN germinal centres (33.3% ±3.0 CD4+ cells co-express PD1 and ICOS) and more closely resembled the interfollicular areas of the normal reactive LN, where 0.71% ±0.23 CD4+ cells co-express PD1 and ICOS (n=6). As PD1 is expressed on chronically activated T cells, we next sought evidence for CLL T cell antigen-specificity. LN-FNA and matching peripheral blood (PB) CD4+ T cells from 6 CLL patients were sorted into PD1hi and PD1lo subsets and subject to spectratyping of their T cell receptor Vβ (TCRVβ) repertoire. Diversity was then assessed using an arbitrary scale in which a higher value indicated a loss of TCR diversity. There was a significant reduction in TCR diversity observed in the PD1hi subset in both LN and PB compartments compared to PD1lo T-cells (PB PD1hi vs PD1lo; 19.83 +/- 1.62 vs 14.67 +/- 2.42; p=0.0049; LN PD1hi vs PD1lo - 21.33+/-0.56 vs 16.00+/- 1.77; p=0.022). Importantly, CLL PB PD1hi cells were also shown to have a significantly reduced TCR diversity compared to PB PD1hi cells from normal age-matched controls (19.83+/-1.62 vs 12.67+/-2.54; p=0.039; n=6). TCR oligoclonality observed in the CLL LN and PB PD1hi CD4 T cells strongly supports the role of antigen in maintaining these two populations. Since PD1hi cells were far more frequent in the CLL LN than blood, these antigen driven interactions likely occur within the LN. In order to look for further evidence of CLL LN T cell antigen-specificity we then performed high throughput TCRVβ CDR3 sequencing (Illumina Genome Analyser, analysed by Immunoseq; Adaptive Biotechnologies) of CLL LN-FNA and PB CD4+ cells. Analysis of TCR sequences obtained from two separate LN and matching PB samples sampled concurrently from the same individual (n=4 patients) revealed that there is a significantly higher commonality in TCR CDR3 clonotypes between two matching LN samples then between any LN and its matching PB sample (p=0.016). These results support the theory that the CLL LN is a site of specific antigen stimulation of CD4+ T cells. Further support for this hypothesis came from the analysis of TCRVβ sequencing results from two sets of two CLL LN and PB samples collected from the same individual 1 month apart. Six persistent TCR CDR3 clonotypes were detected, which were present in all four LN but not in the PB. These clones made up around 1% of the total number of TCR sequences found in each of the LN. In conclusion, our data provides strong new evidence that, just like the neoplastic B cells, CLL LN CD4+ T cells are antigen experienced and that their accumulation in CLL lymph nodes may be antigen-driven. Disclosures: No relevant conflicts of interest to declare.

scholarly journals nef Gene Is Required for Robust Productive Infection by Simian Immunodeficiency Virus of T-Cell-Rich Paracortex in Lymph Nodes

2003 ◽  
Vol 77 (7) ◽  
pp. 4169-4180 ◽  
Author(s):  
Chie Sugimoto ◽  
Kei Tadakuma ◽  
Isao Otani ◽  
Takashi Moritoyo ◽  
Hirofumi Akari ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Lymph Nodes ◽  
Productive Infection ◽  
Lymphoid Tissues ◽  
Double Staining ◽  
Immunodeficiency Virus ◽  
Siv Infection ◽  
Infected Cells ◽  
Sivmac239 Infection

ABSTRACT The pathogenesis of AIDS virus infection in a nonhuman primate AIDS model was studied by comparing plasma viral loads, CD4+ T-cell subpopulations in peripheral blood mononuclear cells, and simian immunodeficiency virus (SIV) infection in lymph nodes for rhesus macaques infected with a pathogenic molecularly cloned SIVmac239 strain and those infected with its nef deletion mutant (Δnef). In agreement with many reports, whereas SIVmac239 infection induced AIDS and depletion of memory CD4+ T cells in 2 to 3 years postinfection (p.i.), Δnef infection did not induce any manifestation associated with AIDS up to 6.5 years p.i. To explore the difference in SIV infection in lymphoid tissues, we biopsied lymph nodes at 2, 8, 72, and 82 weeks p.i. and analyzed them by pathological techniques. Maximal numbers of SIV-infected cells (SIV Gag+, Env+, and RNA+) were detected at 2 weeks p.i. in both the SIVmac239-infected animals and the Δnef-infected animals. In the SIVmac239-infected animals, most of the infected cells were localized in the T-cell-rich paracortex, whereas in the Δnef-infected animals, most were localized in B-cell-rich follicles and in the border region between the paracortex and the follicles. Analyses by double staining of CD68+ macrophages and SIV Gag+ cells and by double staining of CD3+ T cells and SIV Env+ cells revealed that SIV-infected cells were identified as CD4+ T cells in either the SIVmac239 or the Δnef infection. Whereas the many functions of Nef protein were reported from in vitro studies, our finding of SIVmac239 replication in the T-cell-rich paracortex in the lymph nodes supports the reported roles of Nef protein in T-cell activation and enhancement of viral infectivity. Furthermore, the abundance of SIVmac239 infection and the paucity of Δnef infection in the T-cell-rich paracortex accounted for the differences in viral replication and pathogenicity between SIVmac239 and the Δnef mutant. Thus, our in vivo study indicated that the nef gene enhances SIV replication by robust productive infection in memory CD4+ T cells in the T-cell-rich region in lymphoid tissues.

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