Enhanced Antitumor Immunity in Mice Deficient in CD69

Esplugues, Enric; Sancho, David; Vega-Ramos, Javier; Martı́nez-A, Carlos; Syrbe, Uta; Hamann, Alf; Engel, Pablo; Sánchez-Madrid, Francisco; Lauzurica, Pilar

doi:10.1084/jem.20021337

Cited by 159 publications

(177 citation statements)

References 52 publications

(79 reference statements)

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“…A positive correlation between the expression of CXCR4 and CD69 on CD4 T cells and CD8 T cells derived from chronically inflamed liver samples was recently reported [7]. Interestingly, it has recently been shown that CD69 positively regulates TGF-g secretion [40]. This finding may indicate that the CD69/TGF-g / CXCR4 pathway is involved in the retention of recently activated lymphocytes in the liver.…”

Section: Discussionmentioning

confidence: 53%

Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus

Wald¹,

et al. 2004

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Chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is accompanied by inflammation and fibrosis eventually leading to cirrhosis. The chemokine CXCL12 is involved in chronic inflammatory conditions. The role of the CXCL12/CXCR4 pathway in HCV-and HBV-associated liver inflammation and fibrosis was therefore studied. The levels and tissue localization of CXCL12 in liver and plasma of HCV and HBV patients were tested using immunohistochemistry and ELISA. The expression and function of CXCR4 on liver-infiltrating lymphocytes (LIL) were tested by FACS and transwell migration assays. We found that CXCL12 is expressed by bile duct epithelial cells in normal liver tissue. Bile duct proliferation and liver fibrosis in chronic HCV and HBV infection result in the anatomical re-distribution of CXCL12 in the liver. Moreover, CXCL12 is up-regulated in the endothelium of neo-bloodvessels formed in active inflammatory foci and is significantly elevated, compared with controls, in the plasma of patients with advanced liver fibrosis. Complementing these observations were others indicating that over 50% of LIL express CXCR4 and, in response to CXCL12, migrated and adhered to fibronectin. These observations suggest an important role for the CXCL12/CXCR4 pathway in recruitment and retention of immune cells in the liver during chronic HCV and HBV infection.

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Section: Discussionmentioning

confidence: 53%

Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus

Wald¹,

et al. 2004

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“…This suggests that the immunosuppressive effects of FTY720 on collagen-induced arthritis are a result of its antagonistic effects, although it does not exclude possible agonistic effects of FTY720 on endothelial cells for immunosuppression. CD69 expression is induced after activation of mature lymphocytes at inflammatory sites (48)(49)(50)(51)(52)(53) and is required for the production of the anti-inflammatory cytokine, TGF-b, from lymphocytes (54). Furthermore, an exacerbation of collageninduced arthritis due to defective TGF-b production from lymphocytes in the synovium was observed in CD69-deficient mice (55).…”

Section: Discussionmentioning

confidence: 99%

Amelioration of Collagen-Induced Arthritis by a Novel S1P1 Antagonist with Immunomodulatory Activities

Fujii

Hirayama

Ohtake

et al. 2012

The Journal of Immunology

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Sphingosine 1-phosphate (S1P) regulates lymphocyte trafficking through the type 1 sphingosine 1-phosphate receptor (S1P1) and participates in many pathological conditions, including autoimmune diseases. We developed a novel S1P1-selective antagonist, TASP0277308, which is structurally unrelated to S1P. This antagonist competitively inhibited S1P-induced cellular responses, such as chemotaxis and receptor internalization. Furthermore, differing from previously reported S1P1 antagonists, TASP0277308 demonstrated in vivo activities to induce lymphopenia, a block in T cell egress from the thymus, displacement of marginal zone B cells, and upregulation of CD69 expression on both T and B cells, all of which recapitulate phenotypes of S1P1-deficient lymphocytes. In a mouse collagen-induced arthritis model, TASP0277308 significantly suppressed the development of arthritis, even after the onset of disease. These findings provide the first chemical evidence to our knowledge that S1P1 antagonism is responsible for immunosuppression in the treatment of autoimmune diseases and also resolve the discrepancies between genetic and chemical studies on the functions of S1P1 in lymphocytes.

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“…Murine mAb CD69 2.2 (IgG1-j), specific for mouse CD69, was generated as described [9,17,18]. mAb 2.2 was purified from concentrated supernatants obtained in an INTEGRA CL 350 flask (Integra Biosciences AG, Switzerland) using a protein G column (Pharmacia-Biotech, Uppsala, Sweden).…”

Section: Antibodiesmentioning

confidence: 99%

“…In CD69-deficient (CD69 -/-) mouse hematopoietic cell development, thymocyte positive and negative selection and T cell maturation are normal under physiological conditions [8]. Tumor challenge of CD69 -/-mice showed that NK cell-dependent tumor rejection is enhanced in the absence of CD69 [9]. Moreover, CD69 -/-mice, when challenged with antigen, also developed an exacerbated form of collagen-induced arthritis (CIA) [10].…”

Section: Introductionmentioning

confidence: 99%

The role of CD69 in acute neutrophil‐mediated inflammation

et al. 2006

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The leukocyte activation marker CD69 functions as a negative regulator of the immune response, both in NK-dependent tumor rejection and in the inflammation associated with lymphocyte-dependent collagen-induced arthritis. In contrast, it has been reported that CD69-deficient mice are refractory to the neutrophil-dependent acute inflammatory response associated with anti-type II collagen antibody-induced arthritis (CAIA), suggesting a positive regulatory role for CD69 in neutrophil function during arthritis induction. To clarify this discrepancy, the CAIA response was independently analyzed in our CD69-deficient mice. In these experiments, the inflammatory response was unaffected by CD69 deficiency. Additionally, the in vivo down-regulation of CD69 expression by treatment of wild-type mice with the anti-CD69 mAb 2.2, which mimics the CD69-deficient phenotype, did not affect the course of arthritis in this model. Moreover, down-regulation of CD69 expression increased expression in arthritic joints of key inflammatory mediators, including IL-1b, IL-6 and the chemokine MCP-1. Neutrophil accumulation in zymosan-treated air pouches and in thioglycolate-treated peritoneal cavities was also unaffected in CD69-deficient mice. In addition, CD69 expression was absent in activated neutrophils. Taken together, these results rule out a significant stimulatory role for CD69 in acute inflammatory responses mediated by neutrophils.

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Enhanced Antitumor Immunity in Mice Deficient in CD69

Cited by 159 publications

References 52 publications

Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus

Involvement of the CXCL12/CXCR4 pathway in the advanced liver disease that is associated with hepatitis C virus or hepatitis B virus

Amelioration of Collagen-Induced Arthritis by a Novel S1P1 Antagonist with Immunomodulatory Activities

The role of CD69 in acute neutrophil‐mediated inflammation

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