We previously showed that T cells from the mediastinal lymph nodes (MLN) and lung parenchyma of influenza virus-infected mice were functionally remarkably different. Here we demonstrate that the differences in cytokine production are due to differences in the frequencies of T cells within the activated pool able to produce cytokines after TCR stimulation. FACS analysis of T cells from MLN and lung tissue demonstrated that T cells expressing any of the activation markers tested (LFA-1, CD25, CD44, CD45RB, CD49d, CD62L) always expressed high levels of CD44 and LFA-1. These double-high T cells produced >99% of all anti-CD3 mAb-induced IL-4 and IFN-γ. Separation of T cells employing mAb against the other activation markers in combination with anti-CD44 mAb did not enable further fractionation into cytokine producers and nonproducers. Despite their similar phenotype, purified double-high lung parenchyma T cells produced markedly higher levels of IL-2, IL-4, and IFN-γ, and contained a higher frequency of cytokine producers than their MLN counterparts. Activation of the extracellular signal-regulated kinase (ERK)-2 in response to TCR cross-linking was detected in double-high T cells from lung tissue but not MLN. The requirement for ERK signaling for maximal IFN-γ synthesis could nevertheless be demonstrated in both populations by blockade with the inhibitor PD98509. Collectively, the data suggest that inductive and effector sites differ in the frequency of activated T cells able to induce ERK-2-regulated cytokine production after TCR ligation.
|Original language||English (US)|
|Number of pages||10|
|Journal||Journal of Immunology|
|State||Published - Aug 1 1997|
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