TY - JOUR
T1 - Protective CD8 T Cell Memory Is Impaired during Chronic CD70-Driven Costimulation
AU - van Gisbergen, Klaas P. J. M.
AU - van Olffen, Ronald W.
AU - van Beek, Josine
AU - van der Sluijs, Koenraad F.
AU - Arens, Ramon
AU - Nolte, Martijn A.
AU - van Lier, Rene A.
PY - 2009
Y1 - 2009
N2 - Chronic infection results in continuous formation and exhaustion of effector CD8 T cells and in failure of memory CD8 T cell development. Expression of CD70 and other molecules that provide costimulation to T cells is maintained during chronic infection. To analyze the impact of constitutive CD70-driven costimulation, we generated transgenic mice expressing CD70 specifically on T cells. We show that CD70 promoted accumulation of CD8 T cells with characteristics strikingly similar to exhausted effector CD8 T cells found during chronic infection. CD70 on T cells provided costimulation that enhanced primary CD8 T cell responses against influenza. In contrast, memory CD8 T cell maintenance and protection against secondary challenge with influenza was impaired. Interestingly, we found no effect on the formation of either effector or memory CD4 T cells. We conclude that constitutive expression of CD70 is sufficient to deregulate the CD8 T cell differentiation pathway of acute infection reminiscent of events in chronic infection. The Journal of Immunology, 2009, 182: 5352-5362
AB - Chronic infection results in continuous formation and exhaustion of effector CD8 T cells and in failure of memory CD8 T cell development. Expression of CD70 and other molecules that provide costimulation to T cells is maintained during chronic infection. To analyze the impact of constitutive CD70-driven costimulation, we generated transgenic mice expressing CD70 specifically on T cells. We show that CD70 promoted accumulation of CD8 T cells with characteristics strikingly similar to exhausted effector CD8 T cells found during chronic infection. CD70 on T cells provided costimulation that enhanced primary CD8 T cell responses against influenza. In contrast, memory CD8 T cell maintenance and protection against secondary challenge with influenza was impaired. Interestingly, we found no effect on the formation of either effector or memory CD4 T cells. We conclude that constitutive expression of CD70 is sufficient to deregulate the CD8 T cell differentiation pathway of acute infection reminiscent of events in chronic infection. The Journal of Immunology, 2009, 182: 5352-5362
U2 - https://doi.org/10.4049/jimmunol.0802809
DO - https://doi.org/10.4049/jimmunol.0802809
M3 - Article
C2 - 19380782
SN - 0022-1767
VL - 182
SP - 5352
EP - 5362
JO - Journal of immunology (Baltimore, Md.
JF - Journal of immunology (Baltimore, Md.
IS - 9
ER -