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

scholarly journals Combined TLR and CD40 Triggering Induces Potent CD8+ T Cell Expansion with Variable Dependence on Type I IFN

2004 ◽  
Vol 199 (6) ◽  
pp. 775-784 ◽  
Author(s):  
Cory L. Ahonen ◽  
Christie L. Doxsee ◽  
Sean M. McGurran ◽  
Tony R. Riter ◽  
William F. Wade ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Expansion ◽  
Cd8 T Cell ◽  
Secondary Response ◽  
Type I ◽  
Type I Ifn ◽  
Vaccine Adjuvants ◽  
Cell Responses ◽  
T Cell Expansion

Toll-like receptors are important in the activation of innate immunity, and CD40 is a molecule critical for many T and B cell responses. Whereas agonists for either pathway have been used as vaccine adjuvants, we show that a combination of Toll-like receptor (TLR)7 and CD40 agonists synergize to stimulate CD8+ T cell responses 10–20-fold greater than the use of either agonist alone. Antigen-specific CD8+ T cells elicited from combination CD40/TLR7 treatment demonstrated both lytic activities and interferon (IFN)γ production and an enhanced secondary response to antigenic challenge. Agonists for TLRs 2/6, 3, 4, and 9 also synergized with CD40 stimulation, demonstrating that synergy with the CD40 pathway is a property of TLR-derived stimuli in general. The CD8+ T cell expansion induced by CD40/TLR7 triggering was independent of CD4+ T cells, IFNγ, and IL-12 but dependent on B7-mediated costimulation and surprisingly on type I IFN. These studies provide the rational basis for the use of TLR and CD40 agonists together as essential adjuvants to optimize vaccines designed to elicit protective or therapeutic immunity.

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.

Sign in / Sign up

Export Citation Format

Share Document