CXCR5 + CD8 + T cells infiltrate the colorectal tumors and nearby lymph nodes, and are associated with enhanced IgG response in B cells

2017 ◽  
Author(s):  
Junjie Xing ◽  
Chenxin Zhang ◽  
Xiaohong Yang ◽  
Shaoxuan Wang ◽  
Zhongchuan Wang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Colorectal Tumors

scholarly journals Intralymphatic GAD-alum Injection Modulates B Cell Response and Induces Follicular Helper T Cells and PD-1+ CD8+ T Cells in Patients With Recent-Onset Type 1 Diabetes

2022 ◽  
Vol 12 ◽  
Author(s):  
Hugo Barcenilla ◽  
Mikael Pihl ◽  
Jeanette Wahlberg ◽  
Johnny Ludvigsson ◽  
Rosaura Casas
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
B Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Helper T Cells ◽  
Follicular Helper T Cells ◽  
Recent Onset ◽  
Follicular Helper

Antigen-specific immunotherapy is an appealing strategy to preserve beta-cell function in type 1 diabetes, although the approach has yet to meet its therapeutic endpoint. Direct administration of autoantigen into lymph nodes has emerged as an alternative administration route that can improve the efficacy of the treatment. In the first open-label clinical trial in humans, injection of aluminum-formulated glutamic acid decarboxylase (GAD-alum) into an inguinal lymph node led to the promising preservation of C-peptide in patients with recent-onset type 1 diabetes. The treatment induced a distinct immunomodulatory effect, but the response at the cell level has not been fully characterized. Here we used mass cytometry to profile the immune landscape in peripheral blood mononuclear cells from 12 participants of the study before and after 15 months of treatment. The immunomodulatory effect of the therapy included reduction of naïve and unswitched memory B cells, increase in follicular helper T cells and expansion of PD-1+ CD69+ cells in both CD8+ and double negative T cells. In vitro stimulation with GAD65 only affected effector CD8+ T cells in samples collected before the treatment. However, the recall response to antigen after 15 months included induction of CXCR3+ and CD11c+Tbet+ B cells, PD-1+ follicular helper T cells and exhausted-like CD8+ T cells. This study provides a deeper insight into the immunological changes associated with GAD-alum administration directly into the lymph nodes.

scholarly journals A Subset of CXCR5+CD8+ T Cells in the Germinal Centers From Human Tonsils and Lymph Nodes Help B Cells Produce Immunoglobulins

2018 ◽  
Vol 9 ◽  
Author(s):  
Juan Shen ◽  
Xi Luo ◽  
Qiongli Wu ◽  
Jun Huang ◽  
Guanying Xiao ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Germinal Centers

scholarly journals Strong priming of T cells adoptively transferred into scid mice.

1991 ◽  
Vol 174 (6) ◽  
pp. 1653-1656 ◽  
Author(s):  
G H Sunshine ◽  
B L Jimmo ◽  
C Ianelli ◽  
L Jarvis
Keyword(s):  
T Cells ◽  
B Cells ◽  
Lymph Nodes ◽  
Cd8 T Cells ◽  
Scid Mouse ◽  
Interleukin 2 ◽  
Keyhole Limpet Hemocyanin ◽  
Scid Mice

We have examined the requirements for activating unprimed T cells in vivo by transferring T cells into scid mice, which lack mature B and T cells. Purified adult thymocytes and a protein antigen, keyhole limpet hemocyanin (KLH), were injected into scid mice. scid mice injected with T cells and KLH developed cellular lymph nodes containing CD4+ and CD8+ T cells. Cells recovered from the lymph nodes of injected scid mice proliferated and secreted interleukin 2 in response to KLH in vitro. The results indicate that T cells can be primed to KLH in the scid mouse in the absence of B 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 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< 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-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).

Engineered immunostimulatory cells can convert PBMCs from chronic lymphocytic leukemia (CLL) patients into potent tumor killing immune cells.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7517-7517
Author(s):  
Joshua W. Keegan ◽  
Frank Borriello ◽  
Stacey M. Fernandes ◽  
Jennifer R. Brown ◽  
James A. Lederer
Keyword(s):  
T Cells ◽  
B Cells ◽  
Tumor Cell ◽  
Nk Cells ◽  
Cd8 T Cells ◽  
Immune Cells ◽  
Killing Activity ◽  
Tumor Killing ◽  
Tumor Cell Killing ◽  
Potent Tumor

7517 Background: Alloplex Biotherapeutics has developed a cellular therapeutic that uses ENgineered Leukocyte ImmunoSTimulatory cell lines called ENLIST cells to activate and expand populations of tumor killing effector cells from human peripheral blood mononuclear cells (PBMCs). This process leads to a 300-fold expansion of NK cells, CD8+ T cells, NKT cells, and TCRγδ T cells that are called SUPLEXA cells, which will be cryopreserved and transferred back into patients as an autologous immune cell therapy for cancer. In this study, PBMCs from CLL patients were used to generate SUPLEXA cells as a first approach to comparatively profile SUPLEXA cells from cancer patients and normal healthy volunteers (NHVs). Methods: ENLIST cell lines were engineered by expressing curated immunomodulatory proteins in the SK-MEL-2 melanoma cell line. Two million (M) PBMCs from 10 CLL patients or 2 NHVs were incubated with 0.4 M freeze/thaw killed ENLIST cells for 5 days in XVIVO-15 medium with 2% heat-inactivated human AB serum (XAB2) and then split 1:15 in XAB2 containing IL-7 and IL-15 to expand. After 9 days, SUPLEXA cells were harvested and cryopreserved. Results: Original PBMCs and matched SUPLEXA cells from each donor were thawed and characterized by mass cytometry (CyTOF) using a 47-marker antibody panel. CyTOF staining results of PBMCs from CLL patients demonstrated approximately 95% leukemia cells and few T cells, NK cells, B cells, and monocytes. CyTOF staining of SUPLEXA cells from all 10 CLL patients showed expansion of NK cells (17%), CD8 T cells (11%), and CD4 T cells (7.5%) that were similar in phenotype to SUPLEXA cells from NHVs showing high expression of granzymes and perforin that are indicative of potent tumor cell killing activity. Cancer cells in the original CLL PBMC samples were reduced to 0.78%. However, a population of non-T/non-B cells (60% ± 9.5%) was detected in SUPLEXA cells from all CLL patients that require further characterization. Next, SUPLEXA cells from CLL and NHV patients were comparatively tested for tumor cell killing activity at 2:1, 1:1, and 1:2 effector to target cell (MEL-14 melanoma cells expressing RFP) ratios. Percent killing of tumor cells by SUPLEXA cells prepared from CLL patients (77.8% ± 2.6% at 2:1) and NHVs (81.5% ± 0.3% at 2:1) were nearly identical at all effector to target ratios. Conclusions: We demonstrate for the first time that PBMCs from CLL patients can be converted into SUPLEXA cells despite low numbers of normal immune cells at baseline and the known immunologic impairment present in CLL patients. Importantly, SUPLEXA cells derived from CLL patients acquire potent tumor killing activity that is indistinguishable from SUPLEXA cells prepared from NHVs. Taken together, these findings support the feasibility of converting PBMCs from CLL patients with low percentages of NK and T cells into an autologous cellular therapy for cancer.

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