Cutting edge: emergence of CD127high functionally competent memory T cells is compromised by high viral loads and inadequate T cell help.
In this report we have inspected whether difficulties in controlling viral infections negatively impacts the generation of CD127(high) memory T cells. Using both MHC class I and II tetramers we reveal that CD127(low) T cells are not necessarily rapidly deleted but can persist in a pseudoeffector state in which they display the hallmarks of activated effector cells but are functionally inferior. CD127(high) cells can, however, emerge if the infection is contained. We also show that in the absence of CD4 T cell help significant populations of CD127(high) CD8 T cells fail to emerge. Analyses of cytokine-producing activities by both mouse and human CD8 T cells further document that the extended maintenance of T cells in a CD127(low) state has functional consequences which manifest as an impairment of IL-2 production.
Fuller
Michael J
MJ
Department of Microbiology, University of Alabama, Birmingham, AL 35294, USA.
Hildeman
David A
DA
Sabbaj
Steffanie
S
Gaddis
Dalia E
DE
Tebo
Anne E
AE
Shang
Liang
L
Goepfert
Paul A
PA
Zajac
Allan J
AJ
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D017637:Clonal Deletion / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D016867:Immunocompromised Host / Q000235:genetics; D007156:Immunologic Memory / Q000235:genetics; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008216:Lymphocytic Choriomeningitis / Q000276:immunology / Q000473:pathology / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D019562:Viral Load
D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D020395:Receptors, Interleukin-7