Protective CD8 T cell memory is impaired during chronic CD70-driven costimulation.
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.
van Gisbergen
Klaas P J M
KP
Department of Experimental Immunology, Academic Medical Center, Amsterdam, The Netherlands. k.p.vangisbergen@amc.nl
van Olffen
Ronald W
RW
van Beek
Josine
J
van der Sluijs
Koenraad F
KF
Arens
Ramon
R
Nolte
Martijn A
MA
van Lier
Rene A
RA
D000208:Acute Disease; D000818:Animals; D053282:CD27 Ligand / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002908:Chronic Disease; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D007156:Immunologic Memory / Q000235:genetics; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology* / Q000473:pathology*
D053282:CD27 Ligand