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Lymph node transfer

Sarah A Overall, Dorothée Bourges, Ian R van Driel, Paul A Gleeson
How the immune system maintains peripheral tolerance under inflammatory conditions is poorly understood. Here we assessed the fate of gastritogenic T cells following inflammatory activation in vivo. Self-reactive T cells (A23 T cells) specific for the gastric H(+) /K(+) ATPase α subunit (HKα) were transferred into immunosufficient recipient mice and immunised at a site distant to the stomach with adjuvant containing the cognate HKα peptide antigen. Activation of A23 T cells by immunisation did not impact on either immune tolerance or protection from gastric autoimmunity in wild-type BALB/c mice...
October 19, 2016: European Journal of Immunology
Siri Tähtinen, Carolin Blattner, Markus Vähä-Koskela, Dipongkor Saha, Mikko Siurala, Suvi Parviainen, Jochen Utikal, Anna Kanerva, Viktor Umansky, Akseli Hemminki
The immunosuppressive microenvironment of solid tumors renders adoptively transferred T cells hypofunctional. However, adenoviral delivery of immunostimulatory cytokines IL2 and TNFα can significantly improve the efficacy of adoptive T-cell therapy. Using ret transgenic mice that spontaneously develop skin malignant melanoma, we analyzed the mechanism of action of adenoviruses coding for IL2 and TNFα in combination with adoptive transfer of TCR-transgenic TRP-2-specific T cells. Following T-cell therapy and intratumoral virus injection, a significant increase in antigen-experienced, tumor-reactive PD-1 CD8 T cells was seen in both cutaneous lesions and in metastatic lymph nodes...
November 2016: Journal of Immunotherapy
Andrew Gratzon, Jerette Schultz, Kristine Secrest, Kenneth Lee, Jeffrey Feiner, Richard D Klein
ABSTARCT: BACKGROUND: Secondary lymphedema following breast cancer therapy remains a major problem. Vascularized lymph node transfer (VLNT) is a surgical treatment for lymphedema that has shown promising results, but limited studies in the United States have investigated outcomes for single-stage VLNT to the axilla. The goal of this prospective, ongoing study was to investigate the clinical, psychosocial, and functional outcomes of patients who underwent VLNT for the treatment of upper extremity lymphedema after breast cancer therapy...
October 12, 2016: Annals of Surgical Oncology
Yen Leong Chua, Ka Hang Liong, Chiung-Hui Huang, Hok Sum Wong, Qian Zhou, Say Siong Ler, Yafang Tang, Chin Pei Low, Hui Yu Koh, I-Chun Kuo, Yongliang Zhang, W S Fred Wong, Hong Yong Peh, Hwee Ying Lim, Moyar Qing Ge, Angela Haczku, Veronique Angeli, Paul A MacAry, Kaw Yan Chua, David M Kemeny
Previous studies have highlighted the importance of lung-draining lymph nodes in the respiratory allergic immune response, whereas the lung parenchymal immune system has been largely neglected. We describe a new in vivo model of respiratory sensitization to Blomia tropicalis, the principal asthma allergen in the tropics, in which the immune response is focused on the lung parenchyma by transfer of Th2 cells from a novel TCR transgenic mouse, specific for the major B. tropicalis allergen Blo t 5, that targets the lung rather than the draining lymph nodes...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
T G Coursey, F Bian, M Zaheer, S C Pflugfelder, E A Volpe, C S de Paiva
In both humans and animal models, the development of Sjögren syndrome (SS) and non-SS keratoconjunctivitis sicca (KCS) increases with age. Here, we investigated the ocular surface and lacrimal gland (LG) phenotype of NOD.B10.H2(b) mice at 7-14, 45-50, and 96-100 weeks. Aged mice develop increased corneal permeability, CD4(+) T-cell infiltration, and conjunctival goblet cell loss. Aged mice have LG atrophy with increased lymphocyte infiltration and inflammatory cytokine levels. An increase in the frequency of CD4(+)Foxp3(+) T regulatory cells (Tregs) was observed with age in the cervical lymph node (CLN), spleen, and LG...
October 5, 2016: Mucosal Immunology
Jun Xing, Yijun Luo, Xiaoli Wang, Min Gao, Mingping Sun, Xiuping Ding, Tingyong Fan, Jinming Yu
PURPOSE: Definitive chemoradiation therapy remains the standard of care for patients with localized esophageal carcinoma who choose nonsurgical management. However, there is no consensus regarding delineation of the nodal clinical target volume (CTVn), especially for lower cervical lymph nodes. This study aimed to map the location of metastatic supraclavicular lymph nodes in thoracic esophageal carcinoma patients with supraclavicular node involvement and generate an atlas to delineate the CTVn for elective nodal radiation of esophageal squamous cell carcinoma...
2016: OncoTargets and Therapy
Katherine Nutsch, Jiani N Chai, Teresa L Ai, Emilie Russler-Germain, Taylor Feehley, Cathryn R Nagler, Chyi-Song Hsieh
Commensal bacteria shape the colonic regulatory T (Treg) cell population required for intestinal tolerance. However, little is known about this process. Here, we use the transfer of naive commensal-reactive transgenic T cells expressing colonic Treg T cell receptors (TCRs) to study peripheral Treg (pTreg) cell development in normal hosts. We found that T cells were activated primarily in the distal mesenteric lymph node. Treg cell induction was rapid, generating >40% Foxp3(+) cells 1 week after transfer...
September 27, 2016: Cell Reports
Wataru Amano, Saeko Nakajima, Yasuo Yamamoto, Atsuo Tanimoto, Mutsuyoshi Matsushita, Yoshiki Miyachi, Kenji Kabashima
BACKGROUND: Using JAK inhibitors to inhibit cytokine signaling is presumed to be a possible means of treating skin inflammatory disorders such as contact dermatitis. OBJECTIVE: To clarify the action site of JAK inhibitors in skin inflammatory disorders. METHODS: We analyzed the mechanism of action of the JAK inhibitor JTE-052 using murine skin inflammation models, including contact hypersensitivity (CHS) and irritant contact dermatitis. Cells isolated from ear tissue or lymph node (LN) were analyzed by flow cytometry...
September 13, 2016: Journal of Dermatological Science
Xilin Zhang, Jun Gu, Li Zhou, Qing-Sheng Mi
T cell immunoglobulin and mucin-4 (TIM-4), mainly expressed on antigen presenting cells, plays a versatile role in immunoregulation. CD1d-restricted invariant natural killer T (iNKT) cells are potent cells involved in the diverse immune responses. It was recently reported that recombinant TIM-4 (rTIM-4) alone enhanced cytokine production in NKT hybridoma, DN32.D3 cells. Hence, we hypothesized that TIM-4 might regulate iNKT cell biology, especially their function of cytokine secretion. For the first time, we identified that TIM-4 was expressed in thymus iNKT cells, and its expression increased upon iNKT cell migration to the secondary lymphoid organs, especially in lymph nodes...
September 20, 2016: Oncotarget
Amy R Sharkey, Samuel W King, Alexander J Ramsden, Dominic Furniss
INTRODUCTION: Recurrent cellulitis is a frequent and challenging complication of lymphoedema. British Lymphology Society cellulitis guidelines state that decongestive lymphatic therapy reduces the frequency of cellulitis attacks, but do not mention the effect of surgical interventions. This systematic review aims to assess whether surgical interventions for lymphoedema reduce the frequency of attacks of cellulitis. MATERIALS AND METHODS: Embase, Medline, and the Cochrane database were searched for relevant articles from database inception to January 2016...
September 23, 2016: Microsurgery
M Tahara, H Tsuboi, S Segawa, H Asashima, M Iizuka-Koga, T Hirota, H Takahashi, Y Kondo, M Matsui, I Matsumoto, T Sumida
We showed recently that M3 muscarinic acetylcholine receptor (M3R)-reactive CD3(+) T cells play a pathogenic role in the development of murine autoimmune sialadenitis (MIS), which mimics Sjögren's syndrome (SS). The aim of this study was to determine the effectiveness and mechanism of action of retinoic acid-related orphan receptor-gamma t (RORγt) antagonist (A213) in MIS. Splenocytes from M3R knockout (M3R(-/-) ) mice immunized with murine M3R peptide mixture were inoculated into recombination-activating gene 1 knockout (Rag-1(-/-) ) mice (M3R(-/-) →Rag-1(-/-) ) with MIS...
September 19, 2016: Clinical and Experimental Immunology
Tina Chang Albershardt, David James Campbell, Andrea Jean Parsons, Megan Merrill Slough, Jan Ter Meulen, Peter Berglund
We have engineered an integration-deficient lentiviral vector, LV305, to deliver the tumor antigen NY-ESO-1 to human dendritic cells in vivo through pseudotyping with a modified Sindbis virus envelop protein. Mice immunized once with LV305 developed strong, dose-dependent, multifunctional, and cytotoxic NY-ESO-1-specific cluster of differentiation 8 (CD8) T cells within 14 days post-immunization and could be boosted with LV305 at least twice to recall peak-level CD8 T-cell responses. Immunization with LV305 protected mice against tumor growth in an NY-ESO-1-expressing CT26 lung metastasis model, with the protective effect abrogated upon depletion of CD8 T cells...
2016: Molecular Therapy Oncolytics
Mariëtte I E van Poelgeest, Valeria V Visconti, Zohara Aghai, Vanessa J van Ham, Moniek Heusinkveld, Maarten L Zandvliet, A Rob P M Valentijn, Renske Goedemans, Caroline E van der Minne, Els M E Verdegaal, J Baptist M Z Trimbos, Sjoerd H van der Burg, Marij J P Welters
Adoptive transfer of tumor-specific T cells, expanded from tumor-infiltrating lymphocytes or from peripheral blood, is a promising immunotherapeutic approach for the treatment of cancer. Here, we studied whether the tumor-draining lymph nodes (TDLN) of patients with human papillomavirus (HPV)-induced cervical cancer can be used as a source for ACT. The objectives were to isolate lymph node mononuclear cells (LNMC) from TDLN and optimally expand HPV-specific CD4+ and CD8+ T cells under clinical grade conditions...
September 12, 2016: Cancer Immunology, Immunotherapy: CII
Zhenlai Zhu, Yang Luo, Jinlei Yu, Jixin Gao, Yueqiang Zhang, Chunying Xiao, Chen Zhang, Gang Wang, Yufeng Liu, Meng Fu, Xu Yao, Wei Li
Originally recognized as a regulator of axon guidance in the nervous system, Semaphorin 4D (Sema4D, CD100) also participates in various immune responses and many immune-related diseases. However, whether Sema4D is involved in the pathogenesis of contact hypersensitivity (CHS) remains unclear. In this study, we explored the role of Sema4D in oxazolone-induced CHS using Sema4D knockout (KO) mice. We found that Sema4D KO mice developed attenuated CHS responses, as indicated by milder ear-swelling, lower expression of IL-1β, IL-6, CXCL2 and CXCL5, and decreased recruitment of neutrophils, CD8(+) T cells and CD4(+) T cells...
October 2016: Molecular Immunology
Karan Kohli, Anika Janssen, Reinhold Förster
Plasmacytoid dendritic cells (pDCs) have been shown to induce tolerance to innocuous antigens. Their migratory properties allow them to take up antigens from the periphery and transport them to the draining lymph nodes or to the thymus. However, pDC-T-cell interaction in the primary and secondary lymphoid organs still remains poorly defined. In this study, we show that resting pDCs loaded with exogenous antigen could induce tolerance when transferred intralymphatically into a single lymph node of wild-type C57BL/6 mice...
September 4, 2016: European Journal of Immunology
Hiroo Suami, Mario F Scaglioni, Katherine A Dixon, Ramesh C Tailor
BACKGROUND: Vascularized lymph node transfer (VLNT) has become more widespread for surgical treatment of lymphedema. However, interaction between a transferred lymph node and the recipient lymphatic system in relieving lymphedema has not been identified. The aims of this study were to investigate anatomic changes in the lymphatic system in the forelimb of a canine after lymph node dissection and irradiation and to clarify the interaction between the transferred lymph node and recipient lymphatics...
August 2016: Journal of Surgical Research
Séverine Ciré, Sylvie Da Rocha, Maxime Ferrand, Mary K Collins, Anne Galy
Lymph node stromal cells play a role in self-tolerance by presenting tissue antigens to T cells. Yet, immunomodulatory properties of lymphoid tissue stroma, particularly toward CD4+ T cells, remain insufficiently characterized by lack of tools to target antigens for presentation by stromal cells. A lentiviral vector was therefore designed for antigen delivery to MHC class II(+) cells of nonhematopoietic origin. Following intravenous vector delivery, the transgene was detected in lymph node gp38+ stromal cells which were CD45- MHCII+ and partly positive for CD86 and CTLA4 or B7-H4...
October 4, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Katia Urso, David Alvarez, Viviana Cremasco, Kelly Tsang, Angelo Grauel, Robert Lafyatis, Ulrich H von Andrian, Joerg Ermann, Antonios O Aliprantis
Systemic sclerosis (SSc) is a potentially fatal autoimmune disorder with limited therapeutic options. Sclerodermatous graft versus host disease (sclGvHD), induced by transfer of B10.D2 splenocytes into BALB/c Rag2(-/-) mice, models an inflammatory subset of SSc characterized by a prominent IL13-induced gene expression signature in the skin. Host mice deficient in IL4RA, a subunit of the type II IL4/IL13 receptor, are protected from sclGvHD. While IL4RA has a well-established role in Th2 differentiation and alternative macrophage activation, we report here a previously unappreciated function for IL4RA in lymphatic endothelial cells (LECs): regulation of activated T cell egress...
August 4, 2016: JCI Insight
Jiaming Zhu, Weidong Zang, Lu Zang, Yong Li
OBJECTIVE: To investigate the feasibility and safety of uncut Roux-en-Y gastroduodenostomy in totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. METHODS: Clinical data of 30 gastric cancer patients from 4 hospitals undergoing TLDG plus uncut Roux-en-Y gastroduodenostomy from February 2014 to January 2015 were analyzed retrospectively. RESULTS: Among 30 gastric cancer patients, 8 were in Guangdong General Hospital, 9 in The Second Hospital of Jilin University, 4 in Ruijin Hospital and 9 in Fujian Provincial Cancer Hospital, who were diagnosed as distal gastric cancer by pathology without distant metastasis...
August 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
Luyang Zhang, Lu Zang, Junjun Ma, Feng Dong, Zirui He, Minhua Zheng
OBJECTIVE: To evaluate the clinical significance of low ligation of inferior mesenteric artery (IMA) and preservation of left colic artery in laparoscopic radical operation for rectal cancer. METHODS: Clinical data of 103 rectal cancer patients undergoing laparoscopic radical operation in Ruijin Hospital from May 2015 to January 2016 were retrospectively analyzed, including 61 cases with preservation of left colic artery (low ligation group, LL group) and 42 cases without preservation of left colic artery (high ligation group, HL group)...
August 25, 2016: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
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