IL-2 secretion by CD4+ T cells in vivo is rapid, transient, and influenced by TCR-specific competition.
The secretion of IL-2 is a critical and early landmark in the activation program of CD4(+) T cells in vitro, but the lack of sensitive assays has limited its application for studying T cell activation in vivo. Using a mouse cytokine capture assay we were able to detect the rapid secretion of IL-2 after an in vivo stimulus by 1-2 h in naive T cells and as early as 30 min in memory T cells. Maximal secretion was achieved within 1-2 h for memory cells or 6-8 h for naive T cells. Surprisingly IL-2 production terminated quickly in vivo and secretion was undetectable by 20-24 h in either cell type. We further demonstrated that this short duration of secretion can be influenced by cellular competition between Ag-specific CD4(+) T cells. The consequences of competition were mimicked by reducing the strength of the antigenic stimulus. These data argue that early competition between T cells influences both the eventual frequency of IL-2 producers in the population and also the duration of their secretion, potentially by altering the strength or duration of the stimulus available to each T cell.
Sojka
Dorothy K
DK
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Bruniquel
Denis
D
Schwartz
Ronald H
RH
Singh
Nevil J
NJ
D019264:Adoptive Transfer; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002450:Cell Communication / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D004306:Dose-Response Relationship, Immunologic; D004768:Enterotoxins / Q000008:administration & dosage / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
D000942:Antigens, Bacterial; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; C026066:enterotoxin A, Staphylococcal