scholarly journals Immune Mediators in Osteoarthritis: Infrapatellar Fat Pad-Infiltrating CD8+ T Cells Are Increased in Osteoarthritic Patients with Higher Clinical Radiographic Grading

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Jirun Apinun ◽  
Panjana Sengprasert ◽  
Pongsak Yuktanandana ◽  
Srihatach Ngarmukos ◽  
Aree Tanavalee ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Underlying Mechanism ◽  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Immune Mediators ◽  
Adaptive Immune Cells ◽  
Radiographic Grading

Osteoarthritis is a condition of joint failure characterized by many pathologic changes of joint-surrounding tissues. Many evidences suggest the role of both innate and adaptive immunity that interplay, resulting either in initiation or in progression of osteoarthritis. Adaptive immune cells, in particular T cells, have been demonstrated to play a role in the development of OA in animal models. However, the underlying mechanism is yet unclear. Our aim was to correlate the frequency and phenotype of tissue-infiltrating T cells in the synovial tissue and infrapatellar fat pad with radiographic grading. Our results show that CD8+ T cells are increased in osteoarthritic patients with higher radiographic grading. When peripheral blood CD8+ T cells were examined, we show that CD8+ T cells possess a significantly higher level of activation than its CD4+ T cell counterpart (P<0.0001). Our results suggest a role for CD8+ T cells and recruitment of these activated circulating peripheral blood CD8+ T cells to the knee triggering local inflammation within the knee joint.

scholarly journals Interleukin 2 induction of pore-forming protein gene expression in human peripheral blood CD8+ T cells.

1990 ◽  
Vol 171 (4) ◽  
pp. 1269-1281 ◽  
Author(s):  
M J Smyth ◽  
J R Ortaldo ◽  
Y Shinkai ◽  
H Yagita ◽  
M Nakata ◽  
...  
Keyword(s):  
T Cells ◽  
Mrna Expression ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Cytotoxic Lymphocytes ◽  
Mrna Levels ◽  
Cytotoxic Potential

Our studies have analyzed pore-forming protein (PFP) mRNA expression in resting and stimulated human peripheral blood CD3- large granular lymphocytes (LGL), CD3+ T cells, and their CD4+ or CD8+ subsets. Signals that stimulate T cells to develop cytotoxic activity (i.e., IL-2 or OKT-3 mAb) led to the induction of PFP mRNA in T cells. The data indicated that IL-2 directly increased PFP mRNA in the CD8+ subset of T cells, in the absence of new DNA or protein synthesis. Abrogation of IL-2-induced PFP mRNA expression and cytotoxic potential of T cells by the anti-p75 IL-2 receptor mAb suggested that low numbers of p75 IL-2 receptors on CD8+ T cells were capable of transducing signals responsible for these IL-2-induced effects. The induction of T cell PFP mRNA via CD3, using OKT-3 mAb, was less rapid but greater than that caused by IL-2; however, a combination of PMA and ionomycin, which bypasses crosslinking of the TCR/CD3 complex, could not mimic this increase in PFP mRNA levels in T cells. The role of second messenger systems in regulating PFP mRNA expression remains to be determined. In contrast, high constitutive PFP mRNA expression was observed in CD3- LGL and these mRNA levels could not be enhanced by stimulation with IL-2. The cytotoxic potential of peripheral blood T cells and LGL induced in response to IL-2 correlated with IL-2-induced PFP mRNA levels in these cells and was consistent with PFP being one of several important molecules involved in the effector function of cytotoxic lymphocytes.

Role of IL-4-Producing CD8+ T Cells in Patients with Chronic Graft-Versus-Host Disease (cGVHD) and in Normal Healthy Volunteer.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4970-4970
Author(s):  
Kengo Nakamura ◽  
Masashi Takebayashi ◽  
Kenichirou Tajima ◽  
Tsutomu Tanijiri ◽  
Takashi Yokoi ◽  
...  
Keyword(s):  
T Cells ◽  
Healthy Volunteers ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cd4 T Cells ◽  
Cytokine Production ◽  
Chronic Gvhd ◽  
Immunosuppressive Agents ◽  
Surface Marker

Abstract The pathophysiology of cGVHD still remains unclear. To gain more insight into the immunological mechanism of cGVHD, we examined surface marker and cytokine production of peripheral blood T cells from 19 patients in the chronic phase of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The median age of patients was 31 years (range 13–47 years). The median days from allo-HSCT to examination was 43 months (range 17–94 months). Ten patients in whom 6 have treated with immunosuppressive agents and 4 without them developed chronic GVHD, whereas 9 patients in whom 5 have treated with immunosuppressive agents and 4 without them did not develop chronic GVHD. Peripheral blood mononuclear cells were extracted from patients and 10 healthy volunteers, followed by isolation into CD4+ T cells and CD8+ T cells. The analysis of surface marker and intracellular cytokine production of these cells was performed using fluorescence activated cell sorter. The percentage of IFN-g-producing CD8+ T cells among CD8+ T cells was significantly higher in patients with or without cGVHD than in healthy volunteers (p<0.001). Since all 19 patients were in remission, the IFN-g-producing CD8+ T cells might be related to graft-versus-leukemia effect. On the other hand, the percentage of IL-4-producing CD8+ T cells among CD8+ T cells was significantly higher in patients with cGVHD (mean 3.3%, range 1.3–8.2%) than in patients without cGVHD (mean 1.2%, range 0.8–1.7%) and healthy volunteers (mean 1.1%, range 0.1–1.6%) (both p<0.001). By contrast, the percentage of IL-4-producing CD4+ T cells was not different among patients with and without cGVHD and healthy volunteers. Then, we minutely explored the immunological role of IL-4-producing CD8+ T cells in healthy volunteers. These cells expressed the surface marker of CD25, CCR4 and CTLA-4. In the analysis of cytokine production in these cells, we identified the type 2 cytokine, such as IL-4, IL-5, IL-10, and IL-13, although we could not find IFN-g. In conclusion, these findings suggest that IL-4-producing CD8+ T cells may be an immunological marker of cGVHD in which these cells may play a crucial role as regulatory T cells.

B-cell and T-cell values in peripheral blood in Polish mixed-breed rabbits with addition of blood of meet breeds

2014 ◽  
Vol 17 (3) ◽  
pp. 421-426 ◽  
Author(s):  
B. Tokarz-Deptuła ◽  
P. Niedźwiedzka-Rystwej ◽  
B. Hukowska-Szematowicz ◽  
M. Adamiak ◽  
A. Trzeciak-Ryczek ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Laboratory Animals ◽  
Immunological Parameters ◽  
Four Seasons ◽  
Mixed Breed ◽  
The Impact

Abstract In Poland, rabbit is a highly valued animal, due to dietetic and flavour values of its meat, but above all, rabbits tend to be commonly used laboratory animals. The aim of the study was developing standards for counts of B-cells with CD19+ receptor, T-cells with CD5+ receptor, and their subpopulations, namely T-cells with CD4+, CD8+ and CD25+ receptor in the peripheral blood of mixed-breed Polish rabbits with addition of blood of meet breeds, including the assessment of the impact of four seasons of the year and animal sex on the values of the immunological parameters determined. The results showed that the counts of B- and T-cells and their subpopulations in peripheral blood remain within the following ranges: for CD19+ B-cells: 1.05 - 3.05%, for CD5+ T-cells: 34.00 - 43.07%, CD4+ T-cells: 23.52 - 33.23%, CD8+ T-cells: 12.55 - 17.30%, whereas for CD25+ T-cells: 0.72 - 2.81%. As it comes to the season of the year, it was observed that it principally affects the values of CD25+ T-cells, while in the case of rabbit sex, more changes were found in females.

scholarly journals Role of NKG2a/c+CD8+ T cells in pathogenic versus non-pathogenic SIV infections

iScience ◽  
2021 ◽  
Vol 24 (4) ◽  
pp. 102314
Author(s):  
Nicolas Huot ◽  
Philippe Rascle ◽  
Nicolas Tchitchek ◽  
Benedikt Wimmer ◽  
Caroline Passaes ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells

scholarly journals EXTH-14. A NOVEL LONG-ACTING INTERLEUKIN-7 AGONIST, NT-I7, INCREASES CYTOTOXIC CD8 CELLS AND ENHANCES SURVIVAL IN MOUSE GLIOMA MODELS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii89-ii89
Author(s):  
Subhajit Ghosh ◽  
Ran Yan ◽  
Sukrutha Thotala ◽  
Arijita Jash ◽  
Anita Mahadevan ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Cervical Lymph Nodes ◽  
Cd8 Cells ◽  
Interleukin 7 ◽  
Long Acting ◽  
Spleen And Lymph Nodes ◽  
Mouse Glioma

Abstract BACKGROUND Patients with glioblastoma (GBM) are treated with radiation (RT) and temozolomide (TMZ). These treatments can cause prolonged severe lymphopenia, which is associated with shorter survival. NT-I7 (efineptakin alfa) is a long-acting recombinant human IL-7 that supports the proliferation and survival CD4+ and CD8+ cells in both human and mice. We tested whether NT-I7 would protect T cells from treatment-induced lymphopenia and improve survival. METHODS C57BL/6 mice bearing intracranial tumors (GL261 or CT2A) were treated with RT (1.8 Gy/day x 5 days), TMZ (33 mg/kg/day x 5 days) and/or NT-17 (10 mg/kg on the final day of RT completion). We followed for survival and profiled CD3, CD8, CD4, FOXP3 in peripheral blood over time. In parallel, we assessed cervical lymph nodes, bone marrow, thymus, spleen, and the tumor 6 days after NT-I7 treatment. RESULTS Median survival in mice treated with NT-I7 combined with RT was significantly better than RT alone (GL261: 40d vs 34d, p&lt; 0.0021; CT2A: 90d vs 40d, p&lt; 0.0499) or NT-I7 alone (GL261: 40d vs 24d, p&lt; 0.008; CT2A: 90d vs 32d, p&lt; 0.0154). NT-17 with RT was just as effective as NT-I7 combined with RT and TMZ in both GL261 (40d vs 47d) and CT2A (90d vs 90d). NT-I7 treatment significantly increased the amount of CD8+ cells in the peripheral blood and tumor. NT- I7 rescued CD8+ T cells from RT induced lymphopenia in peripheral blood, spleen, and lymph nodes. NT-I7 alone or NT-I7 in combination with RT increased the CD8+ T cells in peripheral blood and tumor while reducing the FOXP3+ T-reg cells in the tumor microenvironment. CONCLUSIONS NT-I7 protects T-cells from RT induced lymphopenia, improves cytotoxic CD8+ T lymphocytes systemically and in the tumor, and improves survival. Presently, a phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).

565 A novel long-acting interleukin-7 agonist, NT-I7, increases cytotoxic CD8+ T cells and enhances survival in mouse glioma models

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A599-A599
Author(s):  
Subhajit Ghosh ◽  
Ran Yan ◽  
Sukrutha Thotala ◽  
Arijita Jash ◽  
Anita Mahadevan ◽  
...  
Keyword(s):  
T Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Standard Of Care ◽  
Control Group ◽  
Cervical Lymph Nodes ◽  
Cd8 Cells ◽  
Interleukin 7 ◽  
Long Acting

BackgroundRadiation (RT) and temozolomide (TMZ), which are standard of care for patients with glioblastoma (GBM), can cause prolonged severe lymphopenia. Lymphopenia, in turn, is an independent risk factor for shorter survival. Interleukin-7 (IL-7) is a cytokine that is required for T cell homeostasis and proliferation. IL-7 levels are inappropriately low in GBM patients with lymphopenia. NT-I7 (efineptakin alfa) is a long-acting recombinant human IL-7 that supports the proliferation and survival CD4+ and CD8+ cells in both human and mice. We tested whether NT-I7 rescues treatment-induced lymphopenia and improves survival.MethodsImmunocompetent C57BL/6 mice bearing two intracranial glioma models (GL261 and CT2A) were treated with RT (1.8 Gy/day x 5 days), TMZ (33 mg/kg/day x 5 days) and/or NT-I7 (10 mg/kg on the final day of RT completion). We profiled the CD3, CD8, CD4, FOXP3 cells in peripheral blood over time. We also immunoprofiled cervical lymph nodes, bone marrow, thymus, spleen, and the tumor 6 days after NT-I7 treatment. Survival was monitored daily.ResultsMedian survival in mice treated with NT-I7 combined with RT was significantly longer than RT alone (GL261: 40d vs 34d, p<0.0021; CT2A: 90d vs 40d, p<0.0499) or NT-I7 alone (GL261: 40d vs 24d, p<0.008; CT2A: 90d vs 32d, p<0.0154). NT-I7 with RT was just as effective as NT-I7 combined with RT and TMZ in both GL261(40d vs 47d) and CT2A (90d vs 90d). Cytotoxic CD8+ T cells were increased in both peripheral blood (0.66 x 105 to 3.34 x 105; P≤0.0001) and tumor (0.53 x 103 to 1.83 x 103; P≤0.0001) in mice treated with NT-I7 when compared to control. Similarly, NT-I7 in combination with RT increased the CD8+ T cells in peripheral blood (0.658 x 105 to 1.839 x 105 P≤0.0001) when compared to RT alone. There were decreases in tumor infiltrating FOXP3+ T-reg cells in mice treated with NT-I7 (1.9 x 104 to 0.75 x 104 P≤0.0001) and NT-I7 + RT (1.9 x 104 to 0.59 x 104 P≤0.0001) when compared to the control group without NT-I7. In addition, NT- I7 treatment increased CD8+ T cells in thymus, spleen, and lymph nodes.ConclusionsNT-I7 enhances cytotoxic CD8+ T lymphocytes systemically and in the tumor microenvironment, and improves survival. A phase I/II trial to evaluate NT-I7 in patients with high-grade gliomas is ongoing (NCT03687957).

Potential role of host effector memory CD8+ T cells in marrow rejection after mixed chimerism induction in cynomolgus monkeys

2010 ◽  
Vol 23 (4) ◽  
pp. 194-203 ◽  
Author(s):  
Kiyoshi Setoguchi ◽  
Hidehiro Kishimoto ◽  
Sakiko Kobayashi ◽  
Hiroaki Shimmura ◽  
Hideki Ishida ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Potential Role ◽  
Mixed Chimerism ◽  
Effector Memory ◽  
Memory Cd8 T Cells ◽  
Cynomolgus Monkeys
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