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Blood, Vol. 94 No. 9 (November 1), 1999:
pp. 2981-2989
Upregulation of Integrin  6/ 1 and Chemokine Receptor CCR1 by
Interleukin-12 Promotes the Migration of Human Type 1 Helper T Cells
Lucia Colantonio,
Andrea Iellem,
Barbara Clissi,
Ruggero Pardi,
Lars Rogge,
Francesco Sinigaglia, and
Daniele D'Ambrosio
From Roche Milano Ricerche, and the Human Immunology
Unit, DIBIT, Milan, Italy.
CD4+ T helper 1 (Th1) cells and Th2 cells are
distinguished based on the pattern of cytokines they are able to
produce. Selectin ligands and chemokine receptors are differentially
expressed in Th1 and Th2 cells, providing a basis for tissue-specific
recruitment of helper T-cell subsets. However, the modes and mechanisms
regulating tissue-specific localization of Th1 and Th2 cells are still
largely unknown. Here, we show the preferential expression on Th1 cells of the integrin  6/ 1, which is distinctly regulated by the
Th1-inducing cytokines interleukin-12 (IL-12) and interferon-alfa
(IFN-). The pattern of integrin 6/1 regulation closely mirrors
that of the chemokine receptor CCR1. Analysis of signal transducer and
activator of transcription 4 (Stat4) activation by IL-12 and IFN-
shows distinct signaling kinetics by these cytokines, correlating with
the pattern of CCR1 and integrin 6/1 expression. Unlike IFN-,
the ability of IL-12 to generate prolonged intracellular signals
appears to be critical for inducing integrin 6/1 upregulation in
Th1 cells. The expression and upregulation of CCR1 and 6/1 integrin promotes the migration of Th1 cells. These findings suggest that the exquisite regulation of integrin 6/1 and CCR1 may play an important role in tissue-specific localization of Th1 cells.
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