scholarly journals L1 Antibodies Block Lymph Node Fibroblastic Reticular Matrix Remodeling In Vivo

1998 ◽  
Vol 187 (12) ◽  
pp. 1953-1963 ◽  
Author(s):  
Gino Di Sciullo ◽  
Tim Donahue ◽  
Melitta Schachner ◽  
Steven A. Bogen

L1 is an immunoglobulin superfamily adhesion molecule highly expressed on neurons and involved in cell motility, neurite outgrowth, axon fasciculation, myelination, and synaptic plasticity. L1 is also expressed by nonneural cells, but its function outside of the nervous system has not been studied extensively. We find that administration of an L1 monoclonal antibody in vivo disrupts the normal remodeling of lymph node reticular matrix during an immune response. Ultrastructural examination reveals that reticular fibroblasts in mice treated with L1 monoclonal antibodies fail to spread and envelop collagen fibers with their cellular processes. The induced defect in the remodeling of the fibroblastic reticular system results in the loss of normal nodal architecture, collapsed cortical sinusoids, and macrophage accumulation in malformed sinuses. Surprisingly, such profound architectural abnormalities have no detectable effects on the primary immune response to protein antigens.

2000 ◽  
Vol 192 (4) ◽  
pp. 475-482 ◽  
Author(s):  
Véronique Moulin ◽  
Fabienne Andris ◽  
Kris Thielemans ◽  
Charlie Maliszewski ◽  
Jacques Urbain ◽  
...  

Increasing evidence indicates that dendritic cells (DCs) are the antigen-presenting cells of the primary immune response. However, several reports suggest that B lymphocytes could be required for optimal T cell sensitization. We compared the immune responses of wild-type and B cell-deficient (μMT) mice, induced by antigen emulsified in adjuvant or pulsed on splenic dendritic cells. Our data show that lymph node cells from both control and μMT animals were primed, but each released distinct cytokine profiles. Lymph node T cells from control animals secreted interferon (IFN)-γ, interleukin (IL)-2, and IL-4, whereas those from μMT mice produced IFN-γ and IL-2 but no IL-4. To test whether B cells may influence the T helper cell type 1 (Th1)/Th2 balance by affecting the function of DCs, we immunized mice by transferring antigen-pulsed DCs from wild-type or mutant mice. Injection of control DCs induced the secretion of IL-4, IFN-γ, and IL-2, whereas administration of DCs from μMT animals failed to sensitize cells to produce IL-4. Analysis of IL-12 production revealed that DCs from μMT mice produce higher levels of IL-12p70 than do DCs from wild-type animals. These data suggest that B lymphocytes regulate the capacity of DCs to promote IL-4 secretion, possibly by downregulating their secretion of IL-12, thereby favoring the induction of a nonpolarized immune response.


1994 ◽  
Vol 645 (1-2) ◽  
pp. 150-156 ◽  
Author(s):  
Alain M. Gardier ◽  
Sébastien Kachaner ◽  
Elisabeth Khan Shaghaghi ◽  
Christian Blot ◽  
Claude Bohuon ◽  
...  

1955 ◽  
Vol 102 (4) ◽  
pp. 379-392 ◽  
Author(s):  
James C. Roberts ◽  
Frank J. Dixon

A secondary immune response to the soluble foreign protein antigens I*BSA and I*BGG has been demonstrated when lymph node cells, largely lymphocytes with a few reticulo-endothelial and plasma cells, from previously immunized rabbits were transferred to x-radiated recipient rabbits, and the recipients then challenged with antigen. The total specific antibody synthesized by the transferred cells during the first 8 days of the secondary response amounted to approximately ⅔ of the wet weight of the transferred cells. In an attempt to elicit a primary response, lymph node cells were obtained from normal, non-immunized donors, and transferred to x-radiated recipients. No immune response was observed upon antigenic stimulation. When normal or previously immunized lymph node cells were incubated with antigen for periods up to 1 hour, washed and injected into recipients, no antibody production was observed.


2013 ◽  
Vol 20 (7) ◽  
pp. 1027-1033 ◽  
Author(s):  
Zhenzhen Ding ◽  
Rongying Ou ◽  
Bing Ni ◽  
Jun Tang ◽  
Yunsheng Xu

ABSTRACTHeat shock proteins (HSPs) have been successfully applied to a broad range of vaccines as biological adjuvants to enhance the immune response. The recently defined HSP110, in particular, exhibits strong protein binding affinity and is capable of enhancing the immunogenicity of protein antigens remarkably more than other HSP family members. In our previous study, we verified that murine HSP110 (mHSP110) significantly enhanced the immune response of a C57BL/6 mouse model to the H-2d-restricted human papillomavirus (HPV) E749-57epitope (short peptide spanning the 49th to 57th amino acid residues in the E7 protein). To determine whether HSP110 similarly enhances the immunogenicity of human epitope peptides, we used theHLA-A2transgenic mouse model to investigate the efficacy of the mHSP110 chaperone molecule as an immunoadjuvant of the human HLA-A2-restricted HPV16 E711-20epitope vaccine. Results showed that mHSP110 efficiently formed a noncovalently bound complex with the E711-20epitope. The mHSP110-E711-20complex induced epitope-specific splenocyte proliferation and E711-20-specific gamma interferon (IFN-γ) secretion. Importantly, cytotoxic T lymphocytes primed by the mHSP110-E711-20complex exerted strong cytolytic effects on target T2cells pulsed with the E711-20peptide or TC-1 cells transfected with theHLA-A2gene. In addition, the mHSP110-E711-20complex elicited strongerex vivoandin vivoantitumor responses than either emulsified complete Freund's adjuvant or HSP70-chaperoned E711-20peptide. These collective data suggest that HSP110 is a promising immunomodulator candidate for peptide-based human cancer vaccines, such as for the HLA-A2-restricted E711-20epitope.


Author(s):  
Pamela A. Aderhold ◽  
Zaynah N. A. Dewan ◽  
Caroline Perner ◽  
Cameron H. Flayer ◽  
Xueping Zhu ◽  
...  

SUMMARYDendritic cells (DCs) of the cDC2 lineage are necessary for the initiation of the allergic immune response and in the dermis are marked by their expression of CD301b. CD301b+ dermal DCs respond to allergens encountered in vivo, but not in vitro. This suggests that another cell in the dermis may sense allergens and relay that information to activate and induce the migration of CD301b+ DCs to the draining lymph node. Using a model of cutaneous allergen exposure, we show that allergens directly activate TRPV1+ sensory neurons leading to itch and pain behaviors. Allergen-activated sensory neurons release the neuropeptide Substance P, which stimulates proximally located CD301b+ DCs through MRGPRA1. Substance P induces CD301b+ DC migration to the draining lymph node where they initiate Th2 differentiation. Thus, sensory neurons act as primary sensors of allergens, linking exposure to activation of allergic-skewing DCs and the initiation of the allergic immune response.


2000 ◽  
Vol 106 (10) ◽  
pp. 1251-1261 ◽  
Author(s):  
Margaret F.C. Callan ◽  
Chrysoula Fazou ◽  
Hongbing Yang ◽  
Tim Rostron ◽  
Kathryn Poon ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Eveline M. Ibeagha-Awemu ◽  
Nathalie Bissonnette ◽  
Suraj Bhattarai ◽  
Mengqi Wang ◽  
Pier-Luc Dudemaine ◽  
...  

Johne’s Disease (JD), caused by Mycobacterium avium subsp paratuberculosis (MAP), is an incurable disease of ruminants and other animal species and is characterized by an imbalance of gut immunity. The role of MAP infection on the epigenetic modeling of gut immunity during the progression of JD is still unknown. This study investigated the DNA methylation patterns in ileal (IL) and ileal lymph node (ILLN) tissues from cows diagnosed with persistent subclinical MAP infection over a one to 4 years period. DNA samples from IL and ILLN tissues from cows negative (MAPneg) (n = 3) or positive for MAP infection (MAPinf) (n = 4) were subjected to whole genome bisulfite sequencing. A total of 11,263 and 62,459 differentially methylated cytosines (DMCs), and 1259 and 8086 differentially methylated regions (DMRs) (FDR<0.1) were found between MAPinf and MAPneg IL and ILLN tissues, respectively. The DMRs were found on 394 genes (denoted DMR genes) in the IL and on 1305 genes in the ILLN. DMR genes with hypermethylated promoters/5′UTR [3 (IL) and 88 (ILLN)] or hypomethylated promoters/5′UTR [10 (IL) and 25 (ILLN)] and having multiple functions including response to stimulus/immune response (BLK, BTC, CCL21, AVPR1A, CHRNG, GABRA4, TDGF1), cellular processes (H2AC20, TEX101, GLA, NCKAP5L, RBM27, SLC18A1, H2AC20BARHL2, NLGN3, SUV39H1, GABRA4, PPA1, UBE2D2) and metabolic processes (GSTO2, H2AC20, SUV39H1, PPA1, UBE2D2) are potential DNA methylation candidate genes of MAP infection. The ILLN DMR genes were enriched for more biological process (BP) gene ontology (GO) terms (n = 374), most of which were related to cellular processes (27.6%), biological regulation (16.6%), metabolic processes (15.4%) and response to stimulus/immune response (8.2%) compared to 75 BP GO terms (related to cellular processes, metabolic processes and transport, and system development) enriched for IL DMR genes. ILLN DMR genes were enriched for more pathways (n = 47) including 13 disease pathways compared with 36 enriched pathways, including 7 disease/immune pathways for IL DMR genes. In conclusion, the results show tissue specific responses to MAP infection with more epigenetic changes (DMCs and DMRs) in the ILLN than in the IL tissue, suggesting that the ILLN and immune processes were more responsive to regulation by methylation of DNA relative to IL tissue. Our data is the first to demonstrate a potential role for DNA methylation in the pathogenesis of MAP infection in dairy cattle.


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