Mesenteric lymph node T cells but not splenic T cells maintain their proliferative response to Concanavalin-A following peroral infection with Toxoplasma gondii

ABSTRACTObservations on the course of Hymenolepis nana infection in immunosuppressed mice are presented. Treatment of the host with hydrocortisone acetate caused superinfection of the bowel with worms and the development of normal cysticercoids in the mesenteric lymph node and liver. Natural infection of mice deprived of their T-cells by pre-adult thymectomy and administration of antithymocyte serum resulted in superinfection and widespread metastasis of aberrant cysticercoids that were greatly enlarged and without scolices, causing death after about five months. The significance of these findings and their possible relevance to human infection with H. nana are discussed.

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Crucial roles of B7-H1 and B7-DC expressed on mesenteric lymph node dendritic cells in the generation of antigen-specific CD4+Foxp3+ regulatory T cells in the establishment of oral tolerance

Blood ◽

10.1182/blood-2009-10-250472 ◽

2010 ◽

Vol 116 (13) ◽

pp. 2266-2276 ◽

Cited By ~ 55

Author(s):

Tomohiro Fukaya ◽

Hideaki Takagi ◽

Yumiko Sato ◽

Kaori Sato ◽

Kawori Eizumi ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

Lymph Node ◽

Regulatory T Cells ◽

Mesenteric Lymph Node ◽

Oral Tolerance ◽

Family Members ◽

T Cell Response ◽

Mesenteric Lymph ◽

B7 Family

Abstract Oral tolerance is a key feature of intestinal immunity, generating systemic tolerance to fed antigens. However, the molecular mechanism mediating oral tolerance remains unclear. In this study, we examined the role of the B7 family members of costimulatory molecules in the establishment of oral tolerance. Deficiencies of B7-H1 and B7-DC abrogated the oral tolerance, accompanied by enhanced antigen-specific CD4+ T-cell response and IgG1 production. Mesenteric lymph node (MLN) dendritic cells (DCs) displayed higher levels of B7-H1 and B7-DC than systemic DCs, whereas they showed similar levels of CD80, CD86, and B7-H2. MLN DCs enhanced the antigen-specific generation of CD4+Foxp3+ inducible regulatory T cells (iTregs) from CD4+Foxp3− T cells rather than CD4+ effector T cells (Teff) relative to systemic DCs, owing to the dominant expression of B7-H1 and B7-DC. Furthermore, the antigen-specific conversion of CD4+Foxp3− T cells into CD4+Foxp3+ iTregs occurred in MLNs greater than in peripheral organs during oral tolerance under steady-state conditions, and such conversion required B7-H1 and B7-DC more than other B7 family members, whereas it was severely impaired under inflammatory conditions. In conclusion, our findings suggest that B7-H1 and B7-DC expressed on MLN DCs are essential for establishing oral tolerance through the de novo generation of antigen-specific CD4+Foxp3+ iTregs.

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Stepwise chromatin and transcriptional acquisition of an intraepithelial lymphocyte program

10.1101/2020.06.04.134650 ◽

2020 ◽

Author(s):

Mariya London ◽

Angelina M. Bilate ◽

Tiago B. R. Castro ◽

Daniel Mucida

Keyword(s):

T Cells ◽

Transcription Factor ◽

Lymph Node ◽

Mesenteric Lymph Node ◽

Trajectory Analysis ◽

Mouse Genetics ◽

Site Specific ◽

Intestinal Lamina Propria ◽

Mesenteric Lymph ◽

Gut Epithelium

AbstractMesenteric lymph node (mLN) T cells undergo tissue adaptation upon migrating to intestinal lamina propria (LP) and intraepithelial (IE) compartments, ensuring appropriate balance between tolerance and resistance. By combining mouse genetics with single-cell and chromatin analyses, we addressed the molecular imprinting of gut epithelium on T cells. Transcriptionally, conventional and regulatory (Treg) CD4+ T cells from mLN, LP and IE segregate based on the gut layer they occupy; trajectory analysis suggests a stepwise loss of CD4-programming and acquisition of an intraepithelial profile. Treg fate–mapping coupled with RNA– and ATAC–sequencing revealed that the Treg program shuts down before an intraepithelial program becomes fully accessible at the epithelium. Ablation of CD4 lineage–defining transcription factor ThPOK results in premature acquisition of an IEL profile by mLN Tregs, partially recapitulating epithelium imprinting. Thus, coordinated replacement of circulating lymphocyte program with site–specific transcriptional and chromatin changes is necessary for tissue imprinting.

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Protective Mucosal Th2 Immune Response against Toxoplasma gondii by Murine Mesenteric Lymph Node Dendritic Cells

Infection and Immunity ◽

10.1128/iai.71.9.5254-5265.2003 ◽

2003 ◽

Vol 71 (9) ◽

pp. 5254-5265 ◽

Cited By ~ 26

Author(s):

Isabelle Dimier-Poisson ◽

Fleur Aline ◽

Marie-Noëlle Mévélec ◽

Céline Beauvillain ◽

Dominique Buzoni-Gatel ◽

...

Keyword(s):

Immune Response ◽

Dendritic Cells ◽

Lymph Node ◽

Toxoplasma Gondii ◽

Mesenteric Lymph Node ◽

Ex Vivo ◽

The Body ◽

Mouse Strains ◽

Mesenteric Lymph ◽

Th2 Immune Response

ABSTRACT Toxoplasma gondii, an obligate intracellular parasite pathogen which initially invades the intestinal epithelium before disseminating throughout the body, may cause severe sequelae in fetuses and life-threatening neuropathy in immunocompromised patients. Immune protection is usually thought to be performed through a systemic Th1 response; considering the route of parasite entry it is important to study and characterize the local mucosal immune response to T. gondii. Despite considerable effort, Toxoplasma-targeted vaccines have proven to be elusive using conventional strategies. We report the use of mesenteric lymph node dendritic cells (MLNDCs) pulsed ex vivo with T. gondii antigens (TAg) as a novel investigation approach to vaccination against T. gondii-driven pathogenic processes. Using a murine model, we demonstrate in two genetically distinct mouse strains (C57BL/6 and CBA/J) that adoptively transferred TAg-pulsed MLNDCs elicit a mucosal Toxoplasma-specific Th2-biased immune response in vivo and confer strong protection against infection. We also observe that MLNDCs mostly traffic to the intestine where they enhance resistance by reduction in the mortality and in the number of brain cysts. Thus, ex vivo TAg-pulsed MLNDCs represent a powerful tool for the study of protective immunity to T. gondii, delivered through its natural route of entry. These findings might impact the design of vaccine strategies against other invasive microorganisms known to be delivered through digestive tract.

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Lactobacillus reuteri DSM 17938 Changes the Frequency of Foxp3+ Regulatory T Cells in the Intestine and Mesenteric Lymph Node in Experimental Necrotizing Enterocolitis

PLoS ONE ◽

10.1371/journal.pone.0056547 ◽

2013 ◽

Vol 8 (2) ◽

pp. e56547 ◽

Cited By ~ 42

Author(s):

Yuying Liu ◽

Nicole Y. Fatheree ◽

Bridgette M. Dingle ◽

Dat Q. Tran ◽

Jon Marc Rhoads

Keyword(s):

T Cells ◽

Lymph Node ◽

Regulatory T Cells ◽

Necrotizing Enterocolitis ◽

Mesenteric Lymph Node ◽

Lactobacillus Reuteri ◽

Mesenteric Lymph

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Protein-bound polysaccharide K augments IL-2 production from murine mesenteric lymph node CD4+ T cells by modulating T cell receptor signaling

Cancer Immunology Immunotherapy ◽

10.1007/s00262-008-0498-1 ◽

2008 ◽

Vol 57 (11) ◽

pp. 1647-1655 ◽

Cited By ~ 10

Author(s):

Hirobumi Asai ◽

Hiroko Iijima ◽

Kenichi Matsunaga ◽

Yoshiharu Oguchi ◽

Hidetoshi Katsuno ◽

...

Keyword(s):

T Cells ◽

Lymph Node ◽

T Cell ◽

T Cell Receptor ◽

Mesenteric Lymph Node ◽

Cell Receptor ◽

Mesenteric Lymph ◽

T Cell Receptor Signaling ◽

Polysaccharide K ◽

Cell Receptor Signaling

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Beneficial effects of Lactobacillus reuteri 6475 on bone density in male mice is dependent on lymphocytes

Scientific Reports ◽

10.1038/s41598-019-51293-8 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Fraser L. Collins ◽

Naiomy Deliz Rios-Arce ◽

Jonathan D. Schepper ◽

A. Daniel Jones ◽

Laura Schaefer ◽

...

Keyword(s):

T Cells ◽

Lymph Node ◽

Bone Density ◽

Mesenteric Lymph Node ◽

Lactobacillus Reuteri ◽

Male Mice ◽

Wild Type ◽

Beneficial Effects ◽

Secreted Factors ◽

Mesenteric Lymph

Abstract Oral treatment with probiotic bacteria has been shown to prevent bone loss in multiple models of osteoporosis. In previous studies we demonstrated that oral administration of Lactobacillus reuteri in healthy male mice increases bone density. The host and bacterial mechanisms of these effects however are not well understood. The objective of this study was to understand the role of lymphocytes in mediating the beneficial effects of L. reuteri on bone health in male mice. We administered L. reuteri in drinking water for 4 weeks to wild type or Rag knockout (lack mature T and B lymphocytes) male mice. While L. reuteri treatment increased bone density in wild type, no significant increases were seen in Rag knockout mice, suggesting that lymphocytes are critical for mediating the beneficial effects of L. reuteri on bone density. To understand the effect of L. reuteri on lymphocytes in the intestinal tissues, we isolated mesenteric lymph node (MLN) from naïve wild type mice. In ex vivo studies using whole mesenteric lymph node (MLN) as well as CD3+ T-cells, we demonstrate that live L. reuteri and its secreted factors have concentration-dependent effects on the expression of cytokines, including anti-inflammatory cytokine IL-10. Fractionation studies identified that the active component of L. reuteri is likely water soluble and small in size (<3 kDa) and its effects on lymphocytes are negatively regulated by a RIP2 inhibitor, suggesting a role for NOD signaling. Finally, we show that T-cells from MLNs treated with L. reuteri supernatants, secrete factors that enhance osterix (transcription factor involved in osteoblast differentiation) expression in MC3T3-E1 osteoblasts. Together, these data suggest that L. reuteri secreted factors regulate T-lymphocytes which play an important role in mediating the beneficial effects of L. reuteri on bone density.

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