Rapid default transition of CD4 T cell effectors to functional memory cells.
The majority of highly activated CD4 T cell effectors die after antigen clearance, but a small number revert to a resting state, becoming memory cells with unique functional attributes. It is currently unclear when after antigen clearance effectors return to rest and acquire important memory properties. We follow well-defined cohorts of CD4 T cells through the effector-to-memory transition by analyzing phenotype, important functional properties, and gene expression profiles. We find that the transition from effector to memory is rapid in that effectors rested for only 3 d closely resemble canonical memory cells rested for 60 d or longer in the absence of antigen. This is true for both Th1 and Th2 lineages, and occurs whether CD4 T cell effectors rest in vivo or in vitro, suggesting a default pathway. We find that the effector-memory transition at the level of gene expression occurs in two stages: a rapid loss of expression of a myriad of effector-associated genes, and a more gradual gain of expression of a cohort of genes uniquely associated with memory cells rested for extended periods.
McKinstry
K Kai
KK
Trudeau Institute, Saranac Lake, NY 12983, USA. kmckinstry@trudeauinstitute.org
Golech
Susanne
S
Lee
Won-Ha
WH
Huston
Gail
G
Weng
Nan-Ping
NP
Swain
Susan L
SL
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005453:Fluorescence; D020869:Gene Expression Profiling; D007156:Immunologic Memory / Q000276:immunology*; D019041:L-Selectin / Q000378:metabolism; D051379:Mice; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
D015415:Biomarkers; D016207:Cytokines; D019041:L-Selectin