A POPULATION OF LYMPHOCYTES BEARING A MEMBRANE RECEPTOR FOR ANTIGEN-ANTIBODY-COMPLEMENT COMPLEXES

A population of lymphoid cells from several animal species, including man, was identified through a membrane receptor which binds sheep red blood cells treated with antibody and complement. When cells from different lymphoid organs were incubated with EAC at 37°C, only part of the lymphocytes (named CRL) bound EAC and formed rosettes, and this interaction was shown to be C3-dependent. Mouse lymphoid cells could be specifically depleted of CRL by allowing them first to interact with EAC and then submitting the mixture to ultracentrifugation in a gradient of BSA. After ultracentrifugation, a population of cells containing 95% or more of non-CRL were recovered from the upper layers of the gradient. In addition to their different abilities to bind EAC, CRL and non-CRL from mouse lymphoid organs could be distinguished by the following properties: (a) CRL adhered preferentially to nylon wool at 37°C in the presence of mouse serum. (b) After differential flotation in a gradient of BSA, a significantly higher proportion of CRL were recovered from the upper layers of the gradient. (c) The population of CRL contained most of the lymphocytes bearing immunoglobulin determinants on their membranes. (d) The distribution of CRL was quite different among lymphocytes obtained from various lymphoid organs, and they were never found in the thymus. (e) The membrane receptor for EAC was not detected in plaque-forming cells of mice which had been previously immunized with burro red cells. CRL and non-CRL could not be distinguished by their life span, as they were found in similar proportions among long-lived and short-lived lymphocytes from mouse peripheral lymph nodes. The function of this receptor on the membrane of certain lymphoid cells may be related to (a) the trapping and localization of antigen in lymphoid organs or (b) the localization of lymphoid cells in inflammatory sites.

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Anatomical Origin of Dendritic Cells Determines Their Life Span in Peripheral Lymph Nodes

The Journal of Immunology ◽

10.4049/jimmunol.165.9.4910 ◽

2000 ◽

Vol 165 (9) ◽

pp. 4910-4916 ◽

Cited By ~ 152

Author(s):

Christiane Ruedl ◽

Pascale Koebel ◽

Martin Bachmann ◽

Michael Hess ◽

Klaus Karjalainen

Keyword(s):

Dendritic Cells ◽

Lymph Nodes ◽

Life Span ◽

Peripheral Lymph

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CCR7-dependent trafficking of RORγ+ ILCs creates a unique microenvironment within mucosal draining lymph nodes

Nature Communications ◽

10.1038/ncomms6862 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 115

Author(s):

Emma C. Mackley ◽

Stephanie Houston ◽

Clare L. Marriott ◽

Emily E. Halford ◽

Beth Lucas ◽

...

Keyword(s):

Lymph Nodes ◽

Lymphoid Cells ◽

Intestinal Cells ◽

Lymphoid Tissues ◽

Mesenteric Lymph Nodes ◽

Cell Responses ◽

Mesenteric Lymph ◽

Peripheral Lymph ◽

Group 3 ◽

Draining Lymph Nodes

Abstract Presentation of peptide:MHCII by RORγ-expressing group 3 innate lymphoid cells (ILC3s), which are enriched within gut tissue, is required for control of CD4 T-cell responses to commensal bacteria. It is not known whether ILC populations migrate from their mucosal and peripheral sites to local draining secondary lymphoid tissues. Here we demonstrate that ILC3s reside within the interfollicular areas of mucosal draining lymph nodes, forming a distinct microenvironment not observed in peripheral lymph nodes. By photoconverting intestinal cells in Kaede mice we reveal constitutive trafficking of ILCs from the intestine to the draining mesenteric lymph nodes, which specifically for the LTi-like ILC3s was CCR7-dependent. Thus, ILC populations traffic to draining lymph nodes using different mechanisms.

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Interferon-alpha induces the expression of the L-selectin homing receptor in human B lymphoid cells.

The Journal of Cell Biology ◽

10.1083/jcb.123.6.1889 ◽

1993 ◽

Vol 123 (6) ◽

pp. 1889-1898 ◽

Cited By ~ 32

Author(s):

S S Evans ◽

R P Collea ◽

M M Appenheimer ◽

S O Gollnick

Keyword(s):

Lymph Nodes ◽

B Cell ◽

Cell Line ◽

Surface Density ◽

Surface Expression ◽

Lymphoid Cells ◽

Homing Receptor ◽

Ifn Alpha ◽

Peripheral Lymph ◽

B Lymphoid

The L-selectin homing receptor expressed by lymphocytes mediates the initial attachment of these cells to high endothelial venules within peripheral lymph nodes. This adhesive interaction is required for the migration of B and T lymphocytes from the blood into peripheral lymph nodes. There is currently little information regarding the nature of the factors involved in the regulation of the synthesis and expression of L-selectin by lymphocytes. In this report, the immunomodulatory cytokine interferon-alpha (IFN-alpha) was shown to markedly upregulate the surface density of L-selectin in the established human B lymphoid Daudi cell line and in a subpopulation of tissue-derived human B lymphoid cells. Other cytokines such as IFN-gamma, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-2, IL-4, IL-6, and low molecular weight B cell growth factor did not affect L-selectin surface expression in the model Daudi B cell line. Upregulation of L-selectin surface density in IFN-alpha-treated Daudi B cells correlated directly with an increase in L-selectin mRNA steady state levels and enhanced L-selectin-dependent binding to a carbohydrate-based ligand, phosphomonoester core polysaccharide. Regulation of L-selectin mRNA by IFN-alpha had characteristics similar to that of classical IFN-stimulated genes including rapid kinetics of induction, protein-synthesis-independent induction, and sensitivity to tyrosine-kinase inhibitors. IFN-alpha did not upregulate L-selectin mRNA levels or surface expression in an IFN-resistant Daudi subclone which exhibits a defect in the signal transduction pathway required for the transcriptional induction of IFN-stimulated genes. These data demonstrate a fundamental role for IFN-alpha in regulating L-selectin synthesis and expression in human B lymphoid cells and suggest a mechanism whereby this cytokine regulates the regional trafficking of B cells to peripheral lymph nodes.

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2257

Journal of Clinical and Translational Science ◽

10.1017/cts.2017.215 ◽

2017 ◽

Vol 1 (S1) ◽

pp. 60-60

Author(s):

Neima Briggs ◽

Leroy Versteeg ◽

Bin Zhan ◽

Rojelio Mejia ◽

Brian Keegan ◽

...

Keyword(s):

Lymph Nodes ◽

Recombinant Proteins ◽

Lymphoid Cells ◽

Effector Memory ◽

Mouse Serum ◽

Mesenteric Lymph Nodes ◽

Endemic Region ◽

Trichuris Muris ◽

Mouse Splenocytes ◽

Vaccine Candidates

OBJECTIVES/SPECIFIC AIMS: Trichuris trichiura, is a leading cause of chronic colitis worldwide, resulting in growth stunting, anemia, and cognitive deficits, predominately in children. Our long-term goal is to develop a vaccine against T. trichiura. Both T. trichiura and the closely related Trichuris muris release excretory/secretory (ES) macromolecules from the stichosome organ, which facilitates intracellular invasion into the cecum. We exploited the high degree of genetic sequence homology between T. trichiura and T. muris to evaluate T. muris stichosome proteins as vaccine candidates. METHODS/STUDY POPULATION: Through immunological screening of the T. muris stichosome cDNA library and T. muris ES macromolecules generated in culture, we identified, cloned, and expressed several vaccine candidates. In ranking these antigens, we selected the most promising recombinant proteins, WAP and CAP-1, and vaccinated AKR mice to evaluate the immunogenicity and efficacy of our candidate. In addition, we collected 240 serum samples in the T. trichiura endemic region of Honduras to measure the recognition of WAP and CAP-1 in naturally infected human. RESULTS/ANTICIPATED RESULTS: We measured a statistically significant reduction in larval worm burden in WAP and ES vaccinated mice, but not CAP-1, by microscopy and real-time PCR of T. muris DNA. We found a significant relationship between antigen-specific IgG1:IgG2a ratio in the mouse serum and degree of protection. Mouse splenocytes, vaccine-sensitized draining lymph nodes, and mesenteric lymph nodes were antigen-stimulated and their secreted Th1, Th2, and Th17 cytokines were measured by Luminex®. Stimulated mouse lymphoid cells were further analysed for T helper, T cytotoxic, and central/effector memory T cells by Flow Cytometry. Human IgG1, IgG2, and IgE antibody titers against WAP and CAP-1 were measured by ELISA. DISCUSSION/SIGNIFICANCE OF IMPACT: In our study, we describe the T cell dependent mechanism of humoral immunity of 2 promising ES-derived vaccines recombinant proteins, WAP and CAP-1. We evaluated the immune response, indicating a driving a Th2-induced humoral response necessary for protection. We further predict protection and allergenicity of WAP in humans using serum from a cohort in an T. trichiura endemic region.

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CXCL12 Mediates CCR7-independent Homing of Central Memory Cells, But Not Naive T Cells, in Peripheral Lymph Nodes

Journal of Experimental Medicine ◽

10.1084/jem.20031645 ◽

2004 ◽

Vol 199 (8) ◽

pp. 1113-1120 ◽

Cited By ~ 83

Author(s):

M. Lucila Scimone ◽

Thomas W. Felbinger ◽

Irina B. Mazo ◽

Jens V. Stein ◽

Ulrich H. von Andrian ◽

...

Keyword(s):

T Cells ◽

Lymph Nodes ◽

Cd8 T Cells ◽

Lymphoid Organs ◽

Central Memory ◽

T Cell Subsets ◽

Naive T Cells ◽

Naïve T Cells ◽

Peripheral Lymph ◽

Secondary Lymphoid Organs

Central memory CD8+ T cells (TCM) confer superior protective immunity against infections compared with other T cell subsets. TCM recirculate mainly through secondary lymphoid organs, including peripheral lymph nodes (PLNs). Here, we report that TCM, unlike naive T cells, can home to PLNs in both a CCR7-dependent and -independent manner. Homing experiments in paucity of lymph node T cells (plt/plt) mice, which do not express CCR7 ligands in secondary lymphoid organs, revealed that TCM migrate to PLNs at ∼20% of wild-type (WT) levels, whereas homing of naive T cells was reduced by 95%. Accordingly, a large fraction of endogenous CD8+ T cells in plt/plt PLNs displayed a TCM phenotype. Intravital microscopy of plt/plt subiliac lymph nodes showed that TCM rolled and firmly adhered (sticking) in high endothelial venules (HEVs), whereas naive T cells were incapable of sticking. Sticking of TCM in plt/plt HEVs was pertussis toxin sensitive and was blocked by anti-CXCL12 (SDF-1α). Anti-CXCL12 also reduced homing of TCM to PLNs in WT animals by 20%, indicating a nonredundant role for this chemokine in the presence of physiologic CCR7 agonists. Together, these data distinguish naive T cells from TCM, whereby only the latter display greater migratory flexibility by virtue of their increased responsiveness to both CCR7 ligands and CXCL12 during homing to PLN.

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Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function.

Journal of Experimental Medicine ◽

10.1084/jem.171.4.979 ◽

1990 ◽

Vol 171 (4) ◽

pp. 979-996 ◽

Cited By ~ 221

Author(s):

R A Daynes ◽

B A Araneo ◽

T A Dowell ◽

K Huang ◽

D Dudley

Keyword(s):

T Cells ◽

T Cell ◽

Lymph Nodes ◽

Steroid Hormones ◽

Lymphoid Tissue ◽

Specific Antigen ◽

Distinct Species ◽

Lymphoid Organs ◽

Lymphoid Cells ◽

Lymphoid Tissues

We investigated the capacity of murine T lymphocytes, isolated from various lymphoid organs of normal or antigen-primed donors, to produce IL-2 or IL-4 after activation with anti-CD3 or specific antigen. Our results established that T cells resident within lymphoid organs being drained by nonmucosal tissue sites (e.g., axillary, inguinal, brachial lymph nodes, or spleen) produced IL-2 as the predominant T cell growth factor (TCGF) after activation. Conversely, activated T cells from lymphoid organs being drained by mucosal tissues (Peyer's patches, and cervical, periaortic, and parathymic lymph nodes) produced IL-4 as the major species of TCGF. Analysis of the lymphoid tissues obtained from adoptive recipients of antigen-primed lymphocytes provided by syngeneic donors provided evidence that direct influences were being exerted on T cells during their residence within defined lymphoid compartments. These lymphoid tissue influences appeared to be responsible for altering the potential of resident T cells to produce distinct species of TCGF. Steroid hormones, known transcriptional enhancers and repressors of specific cellular genes, were implicated in the controlling mechanisms over TCGF production. Glucocorticoids (GCs) were found to exert a systemic effect on all recirculating T cells, evidenced by a marked dominance in IL-4 production by T cells obtained from all lymphoid organs of GC-treated mice, or after a direct exposure of normal lymphoid cells to GCs in vitro before cellular activation with T cell mitogens. Further, the androgen steroid DHEA appeared to be responsible for providing an epigenetic influence to T cells trafficking through peripheral lymphoid organs. This steroid influence resulted in an enhanced potential for IL-2 secretion after activation. Anatomic compartmentalization of the DHEA-facilitated influence appears to be mediated by differential levels of DHEA-sulfatase in lymphoid tissues. DHEA-sulfatase is an enzyme capable of converting DHEA-sulfate (inactive) to the active hormone DHEA. We find very high activities of this enzyme isolated in murine macrophages. The implications of our findings to immunobiology are very great, and indicate that T cells, while clonally restricted for antigen peptide recognition, also appear to exhibit an extreme flexibility with regards to the species of lymphokines they produce after activation. Regulation of this highly conservative mechanism appears to be partially, if not exclusively, controlled by cellular influences being exerted by distinct species of steroid hormones, supplied in an endocrine or a paracrine manner where they mediate either systemic or tissue-localized influences, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

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THE EFFECTS OF THYMUS AND OTHER LYMPHOID ORGANS ENCLOSED IN MILLIPORE DIFFUSION CHAMBERS ON NEONATALLY THYMECTOMIZED MICE

Journal of Experimental Medicine ◽

10.1084/jem.122.3.633 ◽

1965 ◽

Vol 122 (3) ◽

pp. 633-650 ◽

Cited By ~ 50

Author(s):

David Osoba

Keyword(s):

Lymph Nodes ◽

Lymphoid Organs ◽

Lymphoid Cells ◽

Humoral Factor ◽

Immune Reactivity ◽

Apparent Lack ◽

Diffusion Chambers ◽

Cba Mice ◽

Thymus Tissue ◽

Thymectomized Mice

When neonatally thymectomized CBA mice were implanted at 9 to 12 days of age with Millipore diffusion chambers (pore size, 0.1 µ) containing either syngeneic or allogeneic neonatal thymus, they were subsequently found to have the capacity to reject skin homografts and to form antibodies to sheep erythrocytes. In spite of displaying restored immune reactivity, thymectomized mice bearing thymus-filled diffusion chambers still had a lymphopenia and diminished numbers of small lymphocytes in their spleens, lymph nodes and Peyer's patches. Comparison of the lymphoid organs of these mice with those of the thymectomized control mice did not reveal any appreciable difference in the numbers of primary follicles or small lymphocytes. It is postulated that the thymus humoral factor induced immunological competence in lymphoid cells which had left the thymus prior to neonatal thymectomy. The paucity of circulating and tissue small lymphocytes in thymectomized animals, the immune reactivity of which was restored by thymus tissue in diffusion chambers, argues against the theory that the thymus humoral factor has a lymphocytosis-stimulating effect. There was no restoration of immune reactivity in those neonatally thymectomized mice which had been implanted with diffusion chambers containing neonatal or adult spleens, or adult lymph nodes. Thus, the competence-inducing factor is elaborated by the thymus but not by the spleen or lymph nodes. Allogeneic (C57Bl) neonatal thymus tissue, enclosed within diffusion chambers, had the capacity to restore the immune reactivity of totally thymectomized CBA mice, not only to skin homografts of a totally unrelated strain (Ak), but also to grafts isogeneic with the donor of the allogeneic thymus. Therefore, there is no strain barrier to the action of thymus humoral factor. To explain the apparent lack of full participation of thymus lymphocytes in immune reactions it is postulated that thymus lymphocytes are functionally immature in situ, and that they leave the thymus before attaining immunological competence. In the periphery, they undergo further maturation under the influence of the competence-inducing factor produced by the thymus.

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Composition of lymphocyte subpopulations in normal and mildly reactive peripheral lymph nodes in cats

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x211005310 ◽

2021 ◽

pp. 1098612X2110053

Author(s):

Barbara C Rütgen ◽

Elisabeth Baszler ◽

Nicole Weingand ◽

Birgitt Wolfesberger ◽

Daniel Baumgartner ◽

...

Keyword(s):

Lymph Nodes ◽

Reference Data ◽

Pathological Condition ◽

Lymphocyte Subpopulations ◽

Lymphoid Cells ◽

Peripheral Lymph ◽

Positive Antibody ◽

Adult Cats ◽

First Time ◽

Lymphocyte Populations

Objectives Flow cytometric (FCM) immunophenotyping of lymphoid tissue aspirates is an available adjunct for feline lymphoma diagnostics. Reference data have only been established for feline peripheral blood. Studies investigating the composition of normal and mildly reactive feline lymph nodes (LNs) are lacking. The aim of this prospective study was to establish reference data for lymphocyte subpopulations in normal and mildly reactive feline peripheral LNs using a standardised multicolour panel of antibodies. Methods Macroscopically inconspicuous mandibular and/or popliteal LNs from 31 adult cats, which were euthanased for reasons other than haematological diseases, were excised and processed within 5 h after death. Multicolour flow cytometry using eight different feline-specific, anti-canine and human cross-reactive monoclonal antibodies used in current diagnostic marker panels was performed after cytological exclusion of pathological states and complemented by lymphocyte clonality testing, histopathology and immunohistochemistry (IHC) to ensure the absence of lymphoid disease. Results Of 31 cats, the immunophenotyping data of 24 individuals could be included as histopathology and clonality testing excluded a pathological condition. Lymphocyte populations showed the following positive antibody reactions: CD18+ 86.3% ± 13.86%, CD3+ 54.81% ± 11.10%, CD5+ 57.39% ± 12.66%, CD21+ 40.42% ± 12.40%, CD79alphacy+ (CD79αcy) 30.41% ± 13.49% and CD14+ 0.75% ± 1.35%. There were 30.88% ± 13.48% CD4+ and 12.91% ± 6.68% CD8+ cells. Cytology revealed a mixed population of mostly lymphoid cells in all samples. The absence of a monoclonal/oligoclonal neoplastic population was confirmed by lymphocyte clonality testing. Histopathology and IHC showed a normal or mildly reactive pattern in all cases. Conclusions and relevance This study establishes FCM immunophenotyping data of lymphocyte populations of normal and mildly reactive feline peripheral LNs. For the first time, anti-CD5, CD4, CD8 and CD21 reference data in normal and mildly reactive feline peripheral LNs are presented. CD18, CD3, CD14 and CD79αcy have been used to establish reference data for the first time in any feline material.

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