Altered frequency of CD8 + CD11c + T cells and expression of immunosuppressive molecules in lymphoid organs of mouse model of colorectal cancer

2019 ◽  
Vol 234 (7) ◽  
pp. 11986-11998 ◽  
Author(s):  
Davood Rostamzadeh ◽  
Mohammad Reza Haghshenas ◽  
Farhad Daryanoosh ◽  
Mahdi Samadi ◽  
Ahmad Hosseini ◽  
...  
2020 ◽  
Vol 124 ◽  
pp. 218-228
Author(s):  
Rakesh H. Basavalingappa ◽  
Rajkumar Arumugam ◽  
Ninaad Lasrado ◽  
Bharathi Yalaka ◽  
Chandirasegaran Massilamany ◽  
...  

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S33-S34
Author(s):  
Rafael Czepielewski ◽  
Emma Erlich ◽  
Emily Onufer ◽  
Shannon Young ◽  
Ki-Wook Kim ◽  
...  

Abstract Pioneer reports of Crohn’s disease (CD) suggested that impaired lymphatic flow might drive its pathogenesis but remains unsettled. Nodules of tertiary lymphoid organs (TLO) are found in association with collecting lymphatic vessels (CLVs) of the mesentery that normally conducts lymph outflow from the intestine. Whether TLOs affect lymph transport is unknown. In the TNFΔARE mouse model of Crohn’s-like ileitis, TLOs are found in valves regions. Using lymphatic reporters and photoconversion to study cell trafficking from the intestine, our findings indicated that TLOs halts immune cells traveling from the inflamed ileum to the lymph node, effectively trapping DCs, B, and T cells, and impacting the development of microbe tolerogenic regulatory T cells. Lymphatic transport defects were intrinsic to the CLVs because the soluble fluorescent tracer’s passage through TLO was also blocked. Lymph blockage promoted retrograde lymphatic flow returning towards the gut wall due to incapable valves. Moreover, significant lymph leakage was found, specifically at the TLOs. Neutralizing anti-TNF mAb treatment into TNFΔARE mice is ineffective in eliminating TLOs or restoring lymphatic trafficking when administered in female mice with advanced disease. In males, the therapy was able to restore forward flow to the lymph node. However, even in the presence of TNF inhibition, both sexes demonstrated TLO lymph leakage. Thus, mesenteric TLOs that form during chronic ileitis drive broadly impaired lymph transit of molecules and cells from the intestine that is only partially reversible by neutralizing the cytokine cascade underlying the disease and establish a perennial tissue alteration.


2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Scott Tanner ◽  
Stephanie Hill ◽  
Colin Martin ◽  
Robin Lorenz

2002 ◽  
Vol 41 (03) ◽  
pp. 129-134 ◽  
Author(s):  
A. Wolski ◽  
E. Palombo-Kinne ◽  
F. Wolf ◽  
F. Emmrich ◽  
W. Becker ◽  
...  

Summary Aim: The cellular joint infiltrate in rheumatoid arthritis patients is rich in CD4-positive T-helper lymphocytes and macrophages, rendering anti-CD4 monoclonal antibodies (mAbs) suitable for specific immunoscintigraphy of human/ experimental arthritis. Following intravenous injection, however, mAbs are present both in the free form and bound to CD4-positive, circulating monocytes and T-cells. Thus, the present study aimed at analyzing the relative contribution of the free and the cell-bound component to the imaging of inflamed joints in experimental adjuvant arthritis (AA). Methods: AA rat peritoneal macrophages or lymph node T-cells were incubated in vitro with saturating amounts of 99mTc-anti-CD4 mAb (W3/25) and injected i.v. into rats with AA. Results: In vitro release of 99mTc-anti-CD4 mAb from the cells was limited (on average 1.57%/h for macrophages and 0.84%/h for T-cells). Following i.v. injection, whole body/joint scans and tissue measurements showed only negligible accumulation of radioactivity in inflamed ankle joints (tissue: 0.22 and 0.34% of the injected activity, respectively), whereas the radioactivity was concentrated in liver (tissue: 79% and 71%, respectively), kidney, and urinary bladder. Unlike macrophages, however, anti-CD4 mAb-coated T-cells significantly accumulated in lymphoid organs, the inflamed synovial membrane of the ankle joints, as well as in elbow and knee joints. Conclusion: While the overall contribution of cell-bound mAbs to the imaging of arthritic joints with anti-CD4 mAbs is minimal, differential accumulation of macrophages and T-cells in lymphoid organs and the inflamed synovial membrane indicates preferential migration patterns of these 2 cell populations in arthritic rats. Although only validated for 99mTc-anti-CD4 mAbs, extrapolation of the results to other anticellular mAbs with similar affinity for their antigen may be possible.


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