scholarly journals Oversulfated Chondroitin Sulfate Binds to Chemokines and Inhibits Stromal Cell-Derived Factor-1 Mediated Signaling in Activated T Cells

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e94402 ◽  
Author(s):  
Zhao-Hua Zhou ◽  
Elena Karnaukhova ◽  
Mohsen Rajabi ◽  
Kelly Reeder ◽  
Trina Chen ◽  
...  
Keyword(s):  
T Cells ◽  
Chondroitin Sulfate ◽  
Stromal Cell ◽  
Activated T Cells ◽  
Oversulfated Chondroitin Sulfate ◽  
Stromal Cell Derived Factor

scholarly journals Stromal mesenteric lymph node cells are essential for the generation of gut-homing T cells in vivo

2008 ◽  
Vol 205 (11) ◽  
pp. 2483-2490 ◽  
Author(s):  
Swantje I. Hammerschmidt ◽  
Manuela Ahrendt ◽  
Ulrike Bode ◽  
Benjamin Wahl ◽  
Elisabeth Kremmer ◽  
...  
Keyword(s):  
T Cells ◽  
Stromal Cell ◽  
Tissue Tropism ◽  
Mesenteric Lymph Nodes ◽  
Activated T Cells ◽  
Mesenteric Lymph ◽  
In Vitro Activation ◽  
Lymph Node Cells

T cells primed in the gut-draining mesenteric lymph nodes (mLN) are imprinted to express α4β7-integrin and chemokine receptor CCR9, thereby enabling lymphocytes to migrate to the small intestine. In vitro activation by intestinal dendritic cells (DC) or addition of retinoic acid (RA) is sufficient to instruct expression of these gut-homing molecules. We report that in vivo stroma cells, but not DC, allow the mLN to induce the generation of gut tropism. Peripheral LN (pLN) transplanted into the gut mesenteries fail to support the generation of gut-homing T cells, even though gut-derived DC enter the transplants and prime T cells. DC that fail to induce α4β7-integrin and CCR9 in vitro readily induce these factors in vivo upon injection into mLN afferent lymphatics. Moreover, uniquely mesenteric but not pLN stroma cells express high levels of RA-producing enzymes and support induction of CCR9 on activated T cells in vitro. These results demonstrate a hitherto unrecognized contribution of stromal cell delivered signals, including RA, on the imprinting of tissue tropism in vivo.

Blocking the Expression of CD33 Enhances Chemotaxis of Activated T Lymphocytes Generated from AML Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3862-3862
Author(s):  
Rui-kun Zhong ◽  
Edward D. Ball
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Magnetic Beads ◽  
Immune Therapy ◽  
Biological Significance ◽  
Activated T Cells ◽  
Peptide Analog ◽  
Myeloid Antigens ◽  
Activated T Lymphocytes ◽  
Stromal Cell Derived Factor

Autologous T lymphocytes can be employed for immune therapy of patients with acute myeloid leukemia (AML). In an earlier study (Biol Blood Marrow Transplant2002; 8:557), we found that AML cells can be used as antigen presenting cells to activate and expand T cells in culture with IL-2 and monoclonal antibody (mAb) to CD3. In this study, we found that a substantial proportion of the expanded T cells expressed CD33 (34 ± 16%; range: 8 – 58%; N=11) and CD13 (26 ± 5%; range: 22 – 33%), but not CD14. It is unlikely that the myeloid markers were absorbed onto the activated T cells, since the same expression pattern was observed in cultures with purified T cells from normal donors. A literature review disclosed two reports that also observed co-expression of CD33 on activated T cells from both AML patients and normal controls (Schmidt-Wolf et al, Br J Haematol.1995; 90:512; Nakamura et al, letter in Blood, 1994; 83:1442). We measured the functional capacity of the activated T cells in a 4-hr Cr-51 release assay. Pre-incubation of the T cells with anti-CD33 mAb and/or anti-CD13 mAb did not change the cytotoxicity against AML cells. Also, killing of AML cells was not affected by the depletion of CD33+ or CD13+ activated T cells using magnetic beads. The activated T cells migrated in a chemotactic response to a peptide analog (CTCE-0214) of Stromal cell derived factor-1 (SDF-1) when measured in a trans-well assay. When activated T cells were pre-incubated with anti-CD33 mAb, enhanced chemotaxis was observed in response to CTCE-0214 (39.9 ± 0.5% vs 26.9 ± 0.3%, p < 0.001). However, incubation with anti-CD13 mAb did not change the proportion of chemotactic cells. The results of this study confirmed that myeloid antigens can be induced on activated T cells from patients with AML and that there are differences in the mobility of CD33+ T cells in the presence of a chemotactic molecule. Further study of the biological significance of CD33 expression on activated T cells in AML and other diseases is warranted.

scholarly journals Signal-Transducing Adaptor Protein-2 Regulates Stromal Cell-Derived Factor-1α-Induced Chemotaxis in T Cells

2009 ◽  
Vol 183 (12) ◽  
pp. 7966-7974 ◽  
Author(s):  
Yuichi Sekine ◽  
Osamu Ikeda ◽  
Satoshi Tsuji ◽  
Chikako Yamamoto ◽  
Ryuta Muromoto ◽  
...  
Keyword(s):  
T Cells ◽  
Stromal Cell ◽  
Adaptor Protein ◽  
Stromal Cell Derived Factor

Stromal cell–derived factor-1α/CXCL12–induced chemotaxis of T cells involves activation of the RasGAP-associated docking protein p62Dok-1

Blood ◽  
2005 ◽  
Vol 105 (2) ◽  
pp. 474-480 ◽  
Author(s):  
Seiichi Okabe ◽  
Seiji Fukuda ◽  
Young-June Kim ◽  
Masaru Niki ◽  
Louis M. Pelus ◽  
...  
Keyword(s):  
T Cells ◽  
Tyrosine Phosphorylation ◽  
Intracellular Signaling ◽  
Stromal Cell ◽  
Kinase Inhibitor ◽  
Src Kinase ◽  
Adaptor Protein ◽  
Mitogen Activated Protein ◽  
Associated Proteins ◽  
Stromal Cell Derived Factor

Abstract Events mediating stromal cell–derived factor-1 (SDF-1α/CXCL12) chemotaxis of lymphocytes are not completely known. We evaluated intracellular signaling through RasGAP-associated protein p62Dok-1 (downstream of tyrosine kinase [Dok-1]) and associated proteins. SDF-1α/CXCL12 stimulated Dok-1 tyrosine phosphorylation and association with RasGAP, adaptor protein p46Nck, and Crk-L in Jurkat T cells. The phosphorylation of Dok-1 was blocked by pretreatment of cells with the src kinase inhibitor PP2. Src kinase family member Lck was implicated. SDF-1α/CXCL12 did not phosphorylate Dok-1 in J.CaM1.6 cells, a Jurkat derivative not expressing Lck, but did phosphorylate Dok-1 in J.CaM1.6 cells expressing Lck. SDF-1α/CXCL12 induced the tyrosine phosphorylation of Pyk2 and the association of Pyk2 with zeta chain–associated protein-70 kilodaltons (Zap-70) and Vav. SDF-1α/CXCL12 enhanced the association of RasGAP with Pyk2. CXCR4–expressing NIH3T3 and Baf3 cells transfected with full-length Dok-1 cDNA were suppressed in their responses to SDF-1α/CXCL12–induced chemotaxis; mitogen-activated protein (MAP) kinase activity was also decreased. Chemotaxis to SDF-1/CXCL12 was significantly enhanced in Dok-1–/– CD4+ and CD8+ splenic T cells. These results implicate Dok-1, Nck, Crk-L, and Src kinases—especially Lck, Pyk2, Zap-70, Vav, and Ras-GAP—in intracellular signaling by SDF-1α/CXCL12, and they suggest that Dok-1 plays an important role in SDF-1α/CXCL12–induced chemotaxis in T cells.

scholarly journals Efficacious immunomodulatory activity of the chemokine stromal cell–derived factor 1 (SDF-1): local secretion of SDF-1 at the tumor site serves as T-cell chemoattractant and mediates T-cell–dependent antitumor responses

Blood ◽  
2002 ◽  
Vol 100 (5) ◽  
pp. 1551-1558 ◽  
Author(s):  
Kyriaki Dunussi-Joannopoulos ◽  
Krystyna Zuberek ◽  
Kathlene Runyon ◽  
Robert G. Hawley ◽  
Anthony Wong ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
T Lymphocyte ◽  
Stromal Cell ◽  
Tumor Rejection ◽  
Therapeutic Interventions ◽  
Immunomodulatory Activity ◽  
Stromal Cell Derived Factor

The chemokine stromal cell–derived factor 1 (SDF-1) is essential for perinatal viability, B lymphopoiesis, and bone marrow myelopoiesis, and is a potent monocyte and T-lymphocyte chemoattractant. Interactions of SDF-1 with its receptor CXCR4 have been implicated in CD34+ cell migration and homing. Here it is shown that human SDF-1β (hSDF-1β) alone secreted by hSDF-1β–transduced tumor cells promotes efficacious antitumor responses. The murine C1498 leukemia and B16F1 melanoma models have been studied. For expression of hSDF-1β by tumor cells (SDF-tumor cells), packaging cell lines secreting retroviruses encoding hSDF-1β have been used. The results demonstrate that 50% (B16F1) and 90% (C1498) of naive mice injected with SDF-tumor cells reject their tumors. Prophylactic vaccination of naive mice with irradiated SDF-tumor cells leads to systemic immunity, and therapeutic vaccination leads to cure of established tumors. Mice that previously rejected live SDF-tumor cells are immune to the rejected tumor but susceptible to another tumor and have in vitro tumor-specific cytotoxic T lymphocyte (CTL) activity. SDF-tumor cells are not rejected by immunodeficientscid mice. Immunohistochemistry shows significant infiltration of SDF-1 tumors by T cells, and in vivo T-cell depletion studies indicate that CD4+ T cells are required for SDF-mediated tumor rejection. In conclusion, the present data suggest that SDF-1/CXCR4 interactions have the potential to regulate efficacious antitumor immune responses; exploitation of these interactions may lead to novel therapeutic interventions.

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