Investigation of human spleen dendritic cell phenotype and distribution reveals evidence of in vivo activation in a subset of organ donors

Blood ◽  
2001 ◽  
Vol 97 (11) ◽  
pp. 3470-3477 ◽  
Author(s):  
Dorian McIlroy ◽  
Christelle Troadec ◽  
Fernanda Grassi ◽  
Assia Samri ◽  
Benoı̂t Barrou ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Marginal Zone ◽  
Rare Event ◽  
Mouse Spleen ◽  
Cell Phenotype ◽  
White Pulp ◽  
Organ Donors ◽  
Human Spleen

Although the mouse spleen dendritic cell (DC) is perhaps the most intensively studied DC type, little has been published concerning its human equivalent. In this report, rare event flow cytometry and in situ immunofluorescence were used to study the surface phenotype and distribution of HLA-DR+CD3−14−16−19− human spleen DC. Spleens from organ donors with different clinical histories were used. Most (81% ± 9%; n = 14) spleen DCs expressed high levels of the integrin CD11c. CD11c+ DCs were distributed in 3 distinct regions—the peri-arteriolar T-cell zones, the B-cell zones, and the marginal zone, where they formed a ring of cells surrounding the white pulp, just inside a ring of CD14+ red pulp macrophages, apparently more regularly organized than the previously described marginating DC population in the mouse spleen. The T-cell zones contained CD86+ DCs, among which a subpopulation expressed CD83. These mature/activated CD86+DCs represented a minority (12% ± 8%) of total spleen DCs in most organ donors: most spleen DCs are immature. In 3 of 18 (17%) donors, however, most (54%-81%) of spleen DCs were CD86+, suggesting that in vivo DC activation had occurred. In one donor, a radical shift in DC distribution from the marginal zone to the T-cell zones was also observed. This activation of spleen DCs in vivo was reminiscent of the effects of experimental microbial product injection in mice, and it seemed to correlate with bacterial infection or multiple trauma.

scholarly journals The Three-dimensional Structure of Human Splenic White Pulp Compartments

2003 ◽  
Vol 51 (5) ◽  
pp. 655-663 ◽  
Author(s):  
Birte Steiniger ◽  
Lars Rüttinger ◽  
Peter J. Barth
Keyword(s):  
T Cell ◽  
T Lymphocytes ◽  
B Cell ◽  
Marginal Zone ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
White Pulp ◽  
Cell Region ◽  
Human Spleen ◽  
Splenic White Pulp

The precise arrangement of B- and T-lymphocytes in the different compartments of the human splenic white pulp is still largely unknown. We therefore performed a 3D reconstruction of 150 serial sections of a representative adult human spleen alternately stained for CD3 and CD20. The results indicate that the T-cell regions of human spleens may be interrupted by B-cell follicles. Therefore, there is no continuous periarteriolar lymphatic T-cell sheath (PALS) around white pulp arterioles. An arteriole may be surrounded by T-lymphocytes at one level, then run across a follicle without any T-cells around, and finally re-enter a T-cell region. T- and B-cell compartments are intricately interdigitated in the human splenic white pulp. CD4+ T-lymphocytes and the typical fibroblasts of the T-cell region may extend as a thin shell at the follicular surface within the marginal zone. On the other hand, IgD++ B-cells continue from the follicular outer marginal zone along the surface of the T-cell region. Our findings indicate that the microanatomy of the splenic white pulp differs between humans and rodents. This may have consequences for the immigration of recirculating lymphocytes and for initial interactions among antigen-specific T- and B-lymphocytes.

scholarly journals Regulation of dendritic cell numbers and maturation by lipopolysaccharide in vivo.

1996 ◽  
Vol 184 (4) ◽  
pp. 1413-1424 ◽  
Author(s):  
T De Smedt ◽  
B Pajak ◽  
E Muraille ◽  
L Lespagnard ◽  
E Heinen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Marginal Zone ◽  
White Pulp ◽  
Bacterial Product ◽  
Stimulatory Capacity ◽  
Lps Treatment ◽  
Cell Stimulatory Capacity

Dendritic cells (DC) are described as "nature's adjuvant," since they have the capacity to sensitize T cells in vivo upon first encounter with the antigen. The potent accessory properties of DC appear to develop sequentially. In particular, the ability to process antigens and to sensitize native T cells develops in sequence, a process termed "maturation" that is well described in vitro. Here, we obtain evidence for maturation in vivo in response to the bacterial product lipopolysaccharide (LPS). Before LPS treatment, many DC are found at the margin between the red and white pulp. These cells lack the M342 and DEC-205 markers, but process soluble proteins effectively. 6 h after LPS, DC with the M342 and DEC-205 markers are found in increased numbers in the T cell areas. These cells have a reduced capacity to process proteins, but show increases in the B7 costimulator and T cell stimulatory capacity. 48 h after LPS, the number of DC in the spleen is reduced markedly. We interpret these findings to mean that LPS can cause DC in the marginal zone to mature and to migrate into and then out of the T cell areas.

scholarly journals Response of the Splenic Dendritic Cell Population to Malaria Infection

2004 ◽  
Vol 72 (7) ◽  
pp. 4233-4239 ◽  
Author(s):  
Andrew L. Leisewitz ◽  
Kirk A. Rockett ◽  
Bonginkosi Gumede ◽  
Margaret Jones ◽  
Britta Urban ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cell Population ◽  
T Cell Activation ◽  
Malaria Infection ◽  
Cell Activation ◽  
Splenic Dendritic Cell ◽  
Dendritic Cell Population

ABSTRACT Dendritic cells, particularly those residing in the spleen, are thought to orchestrate acquired immunity to malaria, but it is not known how the splenic dendritic cell population responds to malaria infection and how this response compares with the responses of other antigen-presenting cells. We investigated this question for Plasmodium chabaudi AS infection in C57BL/6 mice. We found that dendritic cells, defined here by the CD11c marker, migrated from the marginal zone of the spleen into the CD4+ T-cell area within 5 days after parasites entered the bloodstream. This contrasted with the results observed for the macrophage and B-cell populations, which expanded greatly but did not show any comparable migration. Over the same time period dendritic cells showed upregulation of CD40, CD54, and CD86 costimulatory molecules that are required for successful T-cell activation. In dendritic cells, the peak intracellular gamma interferon expression (as shown by fluorescence-activated cell sorting) was on day 5, 2 days earlier than the peak expression in B-cells or macrophages. These findings show that splenic dendritic cells are actively engaged in the earliest phase of malarial infection in vivo and are likely to be critical in shaping the subsequent immune response.

scholarly journals TAILORED DC INDUCE PROTECTIVE HIV-1 SPECIFIC POLYFUNCTIONAL CD8+ T CELLS IN THE LYMPHOID TISSUE FROM HUMANIZED BLT MICE

2021 ◽  
Author(s):  
Marta Calvet-Mirabent ◽  
Daniel T. Claiborne ◽  
Maud Deruaz ◽  
Serah Tanno ◽  
Carla Serra ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Lymphoid Tissue ◽  
White Pulp ◽  
Blt Mice ◽  
Secondary Lymphoid Organs ◽  
The Impact ◽  
Hiv 1

Effective function of CD8+ T cells and enhanced innate activation of dendritic cells (DC) in response to HIV-1 is linked to protective antiviral immunity in controllers. Manipulation of DC targeting the master regulator TANK-binding Kinase 1 (TBK1) might be useful to acquire controller-like properties. Here, we evaluated the impact of TBK1-primed DC inducing protective CD8+ T cell responses in lymphoid tissue and peripheral blood and their association with reduced HIV-1 disease progression in vivo in the humanized bone marrow, liver and thymus (hBLT) mouse model. A higher proportion of hBLT-mice vaccinated with TBK1-primed DC exhibited less severe CD4+ T cell depletion following HIV-1 infection compared to control groups. This was associated with infiltration of CD8+ T cells in the white pulp from the spleen, reduced spread of infected p24+ cells to secondary lymphoid organs and with preserved abilities of CD8+ T cells from the spleen and blood of vaccinated animals to induce specific polyfunctional responses upon antigen stimulation. Therefore, TBK1-primed DC might be an useful tool for subsequent vaccine studies.

CD8α+ mouse spleen dendritic cells do not originate from the CD8α- dendritic cell subset

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 601-604 ◽  
Author(s):  
Shalin Naik ◽  
David Vremec ◽  
Li Wu ◽  
Meredith O'Keeffe ◽  
Ken Shortman
Keyword(s):  
Dendritic Cells ◽  
Dendritic Cell ◽  
Balance Sheet ◽  
Rare Event ◽  
Cell Subset ◽  
Mouse Spleen ◽  
Dendritic Cell Subset

AbstractAlthough previous studies had indicated that the CD8α- and CD8α+ subtypes of murine dendritic cells (DCs) differ in immediate origin, a recent study found that intravenous transfer of CD8α- DCs led to CD8α+ DCs in the spleen several days later, suggesting a direct precursor-product relationship. We have repeated these experiments with a balance sheet approach. We find that though a few CD8α+ DCs can be generated in such experiments, this is a rare event and could be the result of a contaminant precursor. Most of the immediate precursors of CD8α+ DCs are cells that lack the phenotype of a recognizable DC. CD8α- DCs and CD8α+ DCs are not precursor-product related, though these sublineages may be connected further upstream.

scholarly journals Monitoring T cell–dendritic cell interactions in vivo by intercellular enzymatic labelling

Nature ◽  
2018 ◽  
Vol 553 (7689) ◽  
pp. 496-500 ◽  
Author(s):  
Giulia Pasqual ◽  
Aleksey Chudnovskiy ◽  
Jeroen M. J. Tas ◽  
Marianna Agudelo ◽  
Lawrence D. Schweitzer ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Cell Interactions ◽  
Enzymatic Labelling

Distinct Patterns of Systemic Immune Dysregulation in Indolent B Cell Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3780-3780
Author(s):  
Petros Christopoulos ◽  
Dietmar Pfeifer ◽  
Kilian Bartholomé ◽  
Marie Follo ◽  
Paul Fisch ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Immune Dysregulation ◽  
Cell Phenotype ◽  
Cd4 Cells ◽  
Th Cells

Abstract Mutual interactions of the neoplastic clone with the non-neoplastic immune system may influence immune function and the clinical behaviour of lymphoma. Individuals with immunodeficiency or autoimmune diseases have an increased risk for lymphoma development. The immune microenvironment appears to have a major influence on the prognosis of indolent lymphomas. Conversely, leukemic lymphomas may also cause immunodeficiency: In CLL, direct lymphoma-T cell interactions, which may occur ubiquitously, induce defects in T cell functions (Görgün et al., 2005). We demonstrate here a systemic perturbance of cellular immunity in a prospective study in patients with untreated de novo, limited-stage, non-leukemic indolent B cell lymphomas. Calibrated, quantitative flow cytometry showed a significant reduction of circulating T helper (TH) cells in follicular (FL; n=11; p<0.005) and extranodal marginal zone (eMZL; n=7; p<0.05) lymphomas compared to age-matched healthy persons. Naive TH cells were strongest reduced to 51% (p=0.002) in FL and 24% (p=0.002) in eMZL. Regulatory T cells (CD4loCD25hi; CD4+FoxP3+) were affected less (p=0.04). T cell receptor excision circles within CD4+ cells as assessed by quantitative PCR were not altered in lymphoma patients, indicating neither increased increased thymic output nor homeostatic T cell proliferation to compensate the contracted pool of naive T cells. The TH memory compartments, the global numbers and subsets of CD8+ T (TC) cells, NK, and NKT cells were normal. The peripheral lymphocyte composition was altered differently in early CLL (stage Binet A; leukocyte counts < 28/nl; n=9) with increased TH (p=0.04) and TC (p=0.0002) cells. No significant changes in lymphocyte subsets were noted in monoclonal gammopathy of unknown significance (MGUS; n=6). The functional T cell phenotype in vivo was altered in eMZL as indicated by four- and twofold increased HLA-DR+ TH (p<0.02) and TC (p=0.05) cells. This T cell activation may also explain an increased fraction of terminally differentiated (CD45RA+CD27−) TC cells (p<0.05). Qualitatively similar abnormalities were seen in FL, where activated TH cells were more frequent (p<0.005), and in CLL, where activated TC cells were increased (p=0.04), but not in MGUS. Finally, an increased T cell activation may effect senescence, which was evident by elevated fractions of CD57+ and CD28− cells within the TC compartment of FL/eMZL (p<0.05) and CLL (p<0.005) patients. The activated T cell phenotype was paralleled by increased upregulation of activation markers (CD25, OX40, CD95, p<0.005 for each) and proliferation (p<0.005) by purified CD4 cells from FL/eMZL patients in a standardized anti-CD3/anti-CD28 stimulation culture. None of these parameters was significantly aberrant in CLL. Expression of the activation marker CD69, which is downregulated rapidly after T cell activation, was markedly reduced both in vivo and after in vitro stimulation in FL/eMZL. Collectively, these data demonstrate a global, “preactivated” and presenescent state of peripheral T cells in non-leukemic, indolent T cell lymphomas. Finally, a shift towards TH2 cells was evident in FL/eMZL TH stimulation cultures by increased secretion of IL-4 and IL-5 (p=0.01), but not of IL-2, IFNg, IL-10, and TNFa. This cytokine pattern was absent in CLL and MGUS. The TH2 shift, and the qualitative difference in the immune status in FL/eMZL versus CLL was validated by gene expression profiling of stimulated TH cells with Affymetrix U133 arrays. KEGG annotation revealed decreased expression of proximal TCR signalling molecules and TCR/CD28 transduction pathways with the exception of NFAT in FL/eMZL and CLL. Extensive correlative analyses between gene expression profiles and functional data indicated at least two distinct immune dysregulation patterns: A hyperreactivity/TH2 pattern which is operational even in early disease; and a B cell burden-dependent impairment of TCR signalling. The latter pattern predominates in CLL, which has a comparatively high B cell burden in early disease. These data are clinically relevant since we demonstrate in a prospective trial that untreated FL/eMZL patients fail to respond to protective hepatitis B vaccination (p<0.005). Precise definition of functional T cell defects will permit to study the causes, the prognostic influence, and potential reversibility of immune dysregulation patterns in indolent B cell lymphomas.

Sign in / Sign up

Export Citation Format

Share Document