scholarly journals HIV-TB coinfection impairs CD8+T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

2015 ◽  
Vol 45 (9) ◽  
pp. 2529-2541 ◽  
Author(s):  
Guadalupe V. Suarez ◽  
Matías T. Angerami ◽  
María B. Vecchione ◽  
Natalia Laufer ◽  
Gabriela Turk ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Immune Responses ◽  
Cd8 T Cell ◽  
T Cell Differentiation ◽  
And Function

scholarly journals TET2 Regulates CD8+ T Cell Differentiation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1423-1423
Author(s):  
Shannon A. Carty ◽  
Mercy Gohil ◽  
Gary A Koretzky ◽  
Martha S Jordan
Keyword(s):  
Dna Methylation ◽  
T Cells ◽  
Cell Differentiation ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Differentiation ◽  
Tcr Signaling ◽  
Cell Responses ◽  
And Function

Abstract Regulation of DNA methylation is critical for proper T cell differentiation and function. Antigen-specific CD8+ T cells undergo global remodeling of DNA methylation following viral infection, suggesting that DNA methylation may direct antigen-specific T cell responses. TET2 is a member of the Ten-Eleven-Translocation (TET) family, which converts 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC) and subsequent intermediates ultimately leading to DNA demethylation. How TET2 regulates T cell differentiation and function is unknown. Here we demonstrate that TET2 expression is regulated by TCR signaling in primary murine T cells. Furthermore, using a novel flow cytometric assay to measure 5hmC levels on a single cell basis, we find that TCR signaling also regulates TET activity as evidenced by a rapid increase in global 5hmC levels after TCR stimulation that is blunted in TET2-deficient T cells. To determine the role of TET2 in T cell responses, we generated mice deficient in TET2 in the T cell compartment (TET2fl/flCD4Cre+) mice. These mice develop grossly normal thymic and peripheral T cell subsets. Given the regulation of TET2’s expression and activity by TCR stimulation, we used a murine model of acute viral infection, specifically LCMV-Armstrong, to test if TET2 regulates antigen-specific T cell responses in vivo. Following viral challenge, TET2fl/flCD4Cre+ mice have similar antigen-specific CD8+ T cell expansion and effector responses but exhibit significantly enhanced memory CD8+ T cell differentiation compared to control mice. These data demonstrate that TET2 plays a critical role in directing CD8+ T cell differentiation and function. Studies are ongoing to identify specific TET2 regulated genes important in the development of CD8+ T cell memory. Disclosures No relevant conflicts of interest to declare.

scholarly journals The NK receptor KLRG1 is dispensable for virus‐induced NK and CD8 + T‐cell differentiation and function in vivo

2010 ◽  
Vol 40 (5) ◽  
pp. 1303-1314 ◽  
Author(s):  
Carsten Gründemann ◽  
Sabrina Schwartzkopff ◽  
Marie Koschella ◽  
Oliver Schweier ◽  
Christoph Peters ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
T Cell ◽  
Cd8 T Cell ◽  
T Cell Differentiation ◽  
And Function ◽  
Nk Receptor
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