scholarly journals Intratumoral Activation of 41BB Costimulatory Signals Enhances CD8 T Cell Expansion and Modulates Tumor-Infiltrating Myeloid Cells

2020 ◽  
Vol 205 (10) ◽  
pp. 2893-2904
Author(s):  
Patrick Innamarato ◽  
Sarah Asby ◽  
Jennifer Morse ◽  
Amy Mackay ◽  
MacLean Hall ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Expansion ◽  
Myeloid Cells ◽  
Cd8 T Cell ◽  
Costimulatory Signals ◽  
T Cell Expansion

scholarly journals The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Suzanne PM Welten ◽  
Anke Redeker ◽  
Kees LMC Franken ◽  
Jennifer D Oduro ◽  
Ferry Ossendorp ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Cell Expansion ◽  
Costimulatory Molecule ◽  
Cd8 T Cell ◽  
Lymphocytic Choriomeningitis ◽  
Type I ◽  
Costimulatory Signals ◽  
T Cell Expansion

Signals delivered by costimulatory molecules are implicated in driving T cell expansion. The requirements for these signals, however, vary from dispensable to essential in different infections. We examined the underlying mechanisms of this differential T cell costimulation dependence and found that the viral context determined the dependence on CD28/B7-mediated costimulation for expansion of naive and memory CD8+ T cells, indicating that the requirement for costimulatory signals is not imprinted. Notably, related to the high-level costimulatory molecule expression induced by lymphocytic choriomeningitis virus (LCMV), CD28/B7-mediated costimulation was dispensable for accumulation of LCMV-specific CD8+ T cells because of redundancy with the costimulatory pathways induced by TNF receptor family members (i.e., CD27, OX40, and 4-1BB). Type I IFN signaling in viral-specific CD8+ T cells is slightly redundant with costimulatory signals. These results highlight that pathogen-specific conditions differentially and uniquely dictate the utilization of costimulatory pathways allowing shaping of effector and memory antigen-specific CD8+ T cell responses.

Uraemia-induced immune senescence and clinical outcomes in chronic kidney disease patients

2018 ◽  
Vol 35 (4) ◽  
pp. 624-632 ◽  
Author(s):  
Thomas Crépin ◽  
Mathieu Legendre ◽  
Clémence Carron ◽  
Clément Vachey ◽  
Cécile Courivaud ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
T Cells ◽  
T Cell ◽  
Kidney Disease ◽  
Cell Expansion ◽  
Cd8 T Cell ◽  
Immune Senescence ◽  
Thymic Output ◽  
Age Related ◽  
T Cell Expansion

Abstract Background Patients with chronic kidney disease (CKD) are more prone to develop premature age-related diseases. Data on immune senescence are scarce in CKD populations, except in end-stage renal disease and dialysis. We designed a longitudinal prospective study to evaluate immune senescence at different CKD stages and its influence on CKD patient outcomes. Methods Clinical and biological data collections were performed on 222 patients at different CKD stages [1–2 (n = 85), 4 (n = 53) and 5 (n = 84)]. Immune senescence biomarkers were measured by cytometry on T cells (CD28, CD57, CD45RA, CD31, γH2A.X) or by quantitative polymerase chain reaction [relative telomere length (RTL)] on peripheral blood mononuclear cells and analysed according to CKD stages and outcomes. Results CKD was associated with an increase in immune senescence and inflammation biomarkers, as follows: low thymic output (197 ± 25 versus 88 ± 13 versus 73 ± 21 CD4+CD45RA+CD31+ T cells/mm3), an increased proportion of terminally differentiated T cells (CD8+CD28−CD57+) (24 ± 18 versus 32 ± 17 versus 35 ± 19%) restricted to cytomegalovirus-positive patients, telomere shortening (1.11 ± 0.36 versus 0.78 ± 0.24 versus 0.97 ± 0.21 telomere:single copy ratio) and an increase in C-reactive protein levels [median 2.9 (range 1.8–4.9) versus 5.1 (27–9.6) versus 6.2 (3.4–10.5) mg/L]. In multivariate analysis, shorter RTL was associated with death {hazard ratio [HR] 4.12 [95% confidence interval (CI) 1.44–11.75]}. Low thymic output was associated with infections [HR 1.79 (95% CI (1.34–9.58)] and terminally differentiated CD8+ T-cell expansion with a risk of cardiovascular events [CEs; HR 4.86 (95% CI 1.72–13.72)]. Conclusion CKD was associated with premature immune ageing. Each of these alterations increased the risk of specific age-related diseases, such as RTL and death, thymic function and infections and terminally differentiated CD8+ T-cell expansion and CEs.

scholarly journals Interrupting CD28 costimulation before antigen rechallenge affects CD8+T-cell expansion and effector functions during secondary response in mice

2016 ◽  
Vol 46 (7) ◽  
pp. 1644-1655 ◽  
Author(s):  
Monika Fröhlich ◽  
Tea Gogishvili ◽  
Daniela Langenhorst ◽  
Fred Lühder ◽  
Thomas Hünig
Keyword(s):  
T Cell ◽  
Cell Expansion ◽  
Cd8 T Cell ◽  
Secondary Response ◽  
Effector Functions ◽  
Cd28 Costimulation ◽  
T Cell Expansion
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