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The Journal of Immunology, 2004, 172: 6136-6143.
Copyright © 2004 by The American Association of Immunologists

IL-2 Secretion by CD4+ T Cells In Vivo Is Rapid, Transient, and Influenced by TCR-Specific Competition

Dorothy K. Sojka, Denis Bruniquel, Ronald H. Schwartz and Nevil J. Singh1

Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

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.




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