scholarly journals Characterization of local and peripheral immune system in pregnant and non-pregnant ewes

Author(s):  
Laurel D Quirke ◽  
Paul H Maclean ◽  
Neville A Haack ◽  
Sara J Edwards ◽  
Axel Heiser ◽  
...  

Abstract Modulation of the immune system is known to be important for successful pregnancy but how immune function might differ between the lymph nodes draining the reproductive tract and peripheral lymph nodes is not well understood. Additionally, if immune system changes in response to the presence of an embryo during early pregnancy, and if this response differs in local versus peripheral immune tissue, has not been well characterized. To address these questions, we examined expression of genes important for immune function using NanoString technology in the ampulla and isthmus of the oviduct, endometrium, lymph nodes draining the reproductive tract (lumbo-aortic and medial iliac) as well as a peripheral lymph node (axillary), the spleen and circulating immune cells from ewes on day 5 of the estrous cycle or pregnancy. Concentrations of estradiol and progesterone in plasma were also determined. Principal component analysis revealed separation of the local from the peripheral lymph nodes (MANOVA P = 3.245e-08, R 2 = 0.3) as well as separation of tissues from pregnant and non-pregnant animals [lymph nodes (MANOVA P = 2.337e-09, R 2 = 0.5), reproductive tissues (MANOVA P = 2.417e-14, R 2 = 0.47)]. Nine genes were differentially (FDR <0.10) expressed between lymph node types, with clear difference in expression of these genes between the lumbo-aortic and axillary lymph nodes. Expression of these genes in the medial iliac lymph node was not consistently different to either the axillary or the lumbo-aortic lymph node. Expression of IL10RB was increased (P < 0.05) by 24% in the reproductive tissue of the pregnant animals comparing to non-pregnant animals. Analysis of gene categories revealed that expression of genes of the T cell receptor pathway in reproductive tract tissues was associated (P < 0.05) with pregnancy status. In conclusion, assessment of gene expression of reproductive and immune tissue provides evidence for a specialization of the local immune system around the reproductive tract potentially important for successful establishment of pregnancy. Additionally, differences in gene expression patterns in reproductive tissue from pregnant and non-pregnant animals could be discerned as early as day 5 of pregnancy. This was found to be associated with expression of genes important for T-cell function and thus highlights the important role of these cells in early pregnancy.

Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1436-1445 ◽  
Author(s):  
WE Samlowski ◽  
BA Araneo ◽  
MO Butler ◽  
MC Fung ◽  
HM Johnson

The optimum marrow ablative regimen for preparing recipients of bone marrow transplantation (BMT) has not been established. gamma- Irradiation, but not busulfan, produces a characteristic microvascular injury pattern which results in depressed capacity of normal lymphocytes to localize into the lymph nodes of syngeneic murine BMT recipients. Since peripheral lymph nodes are important sites for initiation and amplification of immune responses, the preparative regimen might delay recovery of regionally compartmentalized immune functions after BMT. We evaluated the effects of busulfan and gamma- irradiation on the phenotypic and functional reconstitution of helper T- cell function within the peripheral lymph nodes of BMT recipients. Both marrow ablative regimens caused a protracted delay in regeneration of peripheral lymph node CD4+ T cells. Specific helper T-cell functions, such as contact hypersensitivity and alloantigen responses, remained significantly depressed in the lymph nodes of irradiated mice for prolonged periods (up to 60 weeks). These responses recovered more rapidly in busulfan-treated BMT recipients. In contrast, the capacity of peripheral lymph node T cells to provide “help” for antigen-specific immunoglobulin production was only transiently depressed by either preparative regimen. Our experiments confirm the hypothesis that the marrow ablative regimen, particularly gamma-irradiation, may contribute to the period of immunodeficiency which follows BMT. The pattern of immune recovery observed suggests that preparative total body irradiation (TBI) may selectively depress the regional recovery of the TH1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) secreting] lymphocyte subset.


Blood ◽  
1989 ◽  
Vol 74 (4) ◽  
pp. 1436-1445 ◽  
Author(s):  
WE Samlowski ◽  
BA Araneo ◽  
MO Butler ◽  
MC Fung ◽  
HM Johnson

Abstract The optimum marrow ablative regimen for preparing recipients of bone marrow transplantation (BMT) has not been established. gamma- Irradiation, but not busulfan, produces a characteristic microvascular injury pattern which results in depressed capacity of normal lymphocytes to localize into the lymph nodes of syngeneic murine BMT recipients. Since peripheral lymph nodes are important sites for initiation and amplification of immune responses, the preparative regimen might delay recovery of regionally compartmentalized immune functions after BMT. We evaluated the effects of busulfan and gamma- irradiation on the phenotypic and functional reconstitution of helper T- cell function within the peripheral lymph nodes of BMT recipients. Both marrow ablative regimens caused a protracted delay in regeneration of peripheral lymph node CD4+ T cells. Specific helper T-cell functions, such as contact hypersensitivity and alloantigen responses, remained significantly depressed in the lymph nodes of irradiated mice for prolonged periods (up to 60 weeks). These responses recovered more rapidly in busulfan-treated BMT recipients. In contrast, the capacity of peripheral lymph node T cells to provide “help” for antigen-specific immunoglobulin production was only transiently depressed by either preparative regimen. Our experiments confirm the hypothesis that the marrow ablative regimen, particularly gamma-irradiation, may contribute to the period of immunodeficiency which follows BMT. The pattern of immune recovery observed suggests that preparative total body irradiation (TBI) may selectively depress the regional recovery of the TH1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) secreting] lymphocyte subset.


2016 ◽  
Vol 79 (6) ◽  
pp. 1032-1035 ◽  
Author(s):  
T. S. EDRINGTON ◽  
G. H. LONERAGAN ◽  
K. J. GENOVESE ◽  
D. L. HANSON ◽  
D. J. NISBET

ABSTRACT Utilizing a transdermal method of inoculation developed in our laboratory, the duration of infection of Salmonella in the peripheral lymph nodes of steers was examined. Thirty-six Holstein steers (mean body weight of 137 kg) were inoculated with Salmonella Montevideo (day 0) on each lower leg and both sides of the back and abdomen. Calves were euthanized beginning at 6 h and subsequently on each of days 1, 2, 4, 7, 9, 11, 14, and 21 postinoculation (four animals each time). The subiliac, popliteal, and superficial cervical (prescapular) lymph nodes were collected and cultured (quantitatively and qualitatively) for the challenge strain of Salmonella. The challenge strain was detected via direct culture within the lymph nodes at 6 h postinoculation and on each subsequent necropsy date. Salmonella levels in lymph node were 0.8 to 1.8 log CFU/g. Lymph nodes were generally positive after enrichment culture throughout the experiment. Salmonella elimination appeared to begin approximately 14 days postinoculation. However, elimination was not completed by day 21; therefore, a second experiment was conducted identical to the first except that the time from inoculation to necropsy was extended. Salmonella was recovered via direct culture on each of the necropsy days, and results in general were similar to those of experiment I, except that on days 20, 24, and 28 isolates from serogroups C2 and E1 were identified in addition to the inoculation strain C1 in multiple animals. The data from both experiments indicate that after a single inoculation event, Salmonella would be completely cleared by approximately 28 days. Further research with expanded times between inoculation and necropsy is required for verification.


1997 ◽  
Vol 186 (5) ◽  
pp. 665-672 ◽  
Author(s):  
Kayo Inaba ◽  
Maggie Pack ◽  
Muneo Inaba ◽  
Hiraki Sakuta ◽  
Frank Isdell ◽  
...  

T lymphocytes recirculate continually through the T cell areas of peripheral lymph nodes. During each passage, the T cells survey the surface of large dendritic cells (DCs), also known as interdigitating cells. However, these DCs have been difficult to release from the lymph node. By emphasizing the use of calcium-free media, as shown by Vremec et al. (Vremec, D., M. Zorbas, R. Scollay, D.J. Saunders, C.F. Ardavin, L. Wu, and K. Shortman. 1992. J. Exp. Med. 176:47–58.), we have been able to release and enrich DCs from the T cell areas. The DCs express the CD11c leukocyte integrin, the DEC-205 multilectin receptor for antigen presentation, the intracellular granule antigens which are recognized by monoclonal antibodies M342, 2A1, and MIDC-8, very high levels of MHC I and MHC II, and abundant accessory molecules such as CD40, CD54, and CD86. When examined with the Y-Ae monoclonal which recognizes complexes formed between I-Ab and a peptide derived from I-Eα, the T cell area DCs expressed the highest levels. The enriched DCs also stimulated a T-T hybridoma specific for this MHC II–peptide complex, and the hybridoma underwent apoptosis. Therefore DCs within the T cell areas can be isolated. Because they present very high levels of self peptides, these DCs should be considered in the regulation of self reactivity in the periphery.


2017 ◽  
Vol 3 (2) ◽  
pp. 205511691773018
Author(s):  
Maria Balan ◽  
Aimee Hope ◽  
Joseph Cassidy ◽  
Maureen McCullough ◽  
Peter J O’Brien

Case summary A 5-year-old male neutered domestic shorthair cat was referred with a history of persistent pyrexia, pica, soft faeces, inappetence, intermittent vomiting, mild-to-moderate granulocytosis and mild hypercalcaemia. No significant improvement was noted after antibiotic and corticosteroid treatment, except that the hypercalcaemia resolved. Physical examination, including thoracic auscultation, and abdominal and peripheral lymph node palpation, were unremarkable. On admission, haematology revealed moderate leukocytosis (36.8 × 109/l) with moderate-to-marked eosinophilia (21.3 × 109/l) and marked basophilia (4.04 × 109/l), the latter identified microscopically. Lymphocytes were markedly decreased (0.37 × 109/l). Blood smear examination revealed 58% eosinophils, 28% neutrophils, 11% basophils, 2% monocytes, 1% lymphocytes and marked, diffuse platelet clumping. Biochemistry abnormalities indicated mild pancreatitis, dehydration and anorexia with mildly increased pancreatic lipase, mild hypernatraemia (157 mmol/l), a moderate decrease in urea (3.1 mmol/l) and a slight decrease in phosphate (1.32 mmol/l). Ultrasound and radiographic imaging revealed enlargement of the mesenteric lymph nodes. Fine-needle aspiration, a Tru-cut biopsy and immunohistochemistry were performed. Cytological examination revealed ~65–75% lymphocytes (~80% were larger than a neutrophil), ~25–35% eosinophils and occasional basophils. Lymphocytes had single, small (<1/3 red blood cells), prominent nucleoli and increased pale, mildly vacuolated cytoplasm. On histopathology, cells were monomorphic, large, with prominent nucleoli, and mild, multifocal, staining for T-cell marker CD3. Smaller cells were strongly CD3-positive. Cells were negative for B-cell marker CD45R. Relevance and novel information This is the most severe case of paraneoplastic basophilia reported with feline alimentary T-cell lymphoma with accompanying eosinophilia and lymph node infiltration. Feline basophil prevalence is reported for the first time.


2017 ◽  
Vol 71 (2) ◽  
pp. 174-179 ◽  
Author(s):  
Gregory David Scott ◽  
Susan K Atwater ◽  
Dita A Gratzinger

AimsTo create clinically relevant normative flow cytometry data for understudied benign lymph nodes and characterise outliers.MethodsClinical, histological and flow cytometry data were collected and distributions summarised for 380 benign lymph node excisional biopsies. Outliers for kappa:lambda light chain ratio, CD10:CD19 coexpression, CD5:CD19 coexpression, CD4:CD8 ratios and CD7 loss were summarised for histological pattern, concomitant diseases and follow-up course.ResultsWe generated the largest data set of benign lymph node immunophenotypes by an order of magnitude. B and T cell antigen outliers often had background immunosuppression or inflammatory disease but did not subsequently develop lymphoma.ConclusionsDiagnostic immunophenotyping data from benign lymph nodes provide normative ranges for clinical use. Outliers raising suspicion for B or T cell lymphoma are not infrequent (26% of benign lymph nodes). Caution is indicated when interpreting outliers in the absence of excisional biopsy or clinical history, particularly in patients with concomitant immunosuppression or inflammatory disease.


Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4104-4112 ◽  
Author(s):  
Jean-Marc Gauguet ◽  
Steven D. Rosen ◽  
Jamey D. Marth ◽  
Ulrich H. von Andrian

Abstract Blood-borne lymphocyte trafficking to peripheral lymph nodes (PLNs) depends on the successful initiation of rolling interactions mediated by L-selectin binding to sialomucin ligands in high endothelial venules (HEVs). Biochemical analysis of purified L-selectin ligands has identified posttranslational modifications mediated by Core2GlcNAcT-I and high endothelial cell GlcNAc-6-sulfotransferase (HECGlcNAc6ST). Consequently, lymphocyte migration to PLNs of C2GlcNAcT-I-/- and HEC-GlcNAc6ST-/- mice was reduced; however, B-cell homing was more severely compromised than T-cell migration. Accordingly, intravital microscopy (IVM) of PLN HEVs revealed a defect in B-cell tethering and increased rolling velocity (Vroll) in C2GlcNAcT-I-/- mice that was more pronounced than it was for T cells. By contrast, B- and T-cell tethering was normal in HEC-GlcNAc6ST-/- HEVs, but Vroll was accelerated, especially for B cells. The increased sensitivity of B cells to glycan deficiencies was caused by lower expression levels of L-selectin; L-selectin+/- T cells expressing L-selectin levels equivalent to those of B cells exhibited intravascular behavior similar to that of B cells. These results demonstrate distinct functions for C2GlcNAcT-I and HEC-GlcNAc6ST in the differential elaboration of HEV glycoproteins that set a threshold for the amount of L-selectin needed for lymphocyte homing. (Blood. 2004;104:4104-4112)


2001 ◽  
Vol 114 (19) ◽  
pp. 3463-3477
Author(s):  
Shulamit B. Wallach-Dayan ◽  
Valentin Grabovsky ◽  
Jürgen Moll ◽  
Jonathan Sleeman ◽  
Peter Herrlich ◽  
...  

Cell motility is an essential element of tumor dissemination, allowing organ infiltration by cancer cells. Using mouse LB lymphoma cells transfected with standard CD44 (CD44s) cDNA (LB-TRs cells) or with the alternatively spliced CD44 variant CD44v4-v10 (CD44v) cDNA (LB-TRv cells), we explored their CD44-dependent cell migration. LB-TRv cells, but not LB-TRs or parental LB cells, bound soluble hyaluronic acid (HA) and other glycosaminoglycans (GAGs), and exclusively formed, under physiological shear force, rolling attachments on HA substrate. Furthermore, LB-TRv cells, but not LB-TRs cells or their parental LB cells, displayed accelerated local tumor formation and enhanced accumulation in the peripheral lymph nodes after s.c. inoculation. The aggressive metastatic behavior of i.v.-injected LB-TRV cells, when compared with that of other LB-transfectants, is attributed to more efficient migration to the lymph nodes, rather than to local growth in the lymph node. Injection of anti-CD44 monoclonal antibody or of the enzyme hyaluronidase also prevented tumor growth in lymph nodes of BALB/c mice inoculated with LB-TRv cells. The enhanced in vitro rolling and enhanced in vivo local tumor growth and lymph node invasion disappeared in LB cells transfected with CD44v cDNA bearing a point mutation at the HA binding site, located at the distal end of the molecule constant region. These findings show that the interaction of cell surface CD44v with HA promotes cell migration both in vitro and in vivo, and they contribute to our understanding of the mechanism of cell trafficking, including tumor spread.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1047
Author(s):  
Chiu-Li Yeh ◽  
Sharon Angela Tanuseputero ◽  
Jin-Ming Wu ◽  
Yi-Ru Tseng ◽  
Po-Jen Yang ◽  
...  

This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4+ T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4+ T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4+ T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4+ T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4+ T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis.


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