TY - JOUR
T1 - The CXC chemokine murine monokine induced by IFN-γ (CXC chemokine ligand 9) is made by APCs, targets lymphocytes including activated B cells, and supports antibody responses to a bacterial pathogen in vivo
AU - Park, Matthew K.
AU - Amichay, Doron
AU - Love, Paul
AU - Wick, Elizabeth
AU - Liao, Fang
AU - Grinberg, Alex
AU - Rabin, Ronald L.
AU - Zhang, Hongwei H.
AU - Gebeyehu, Senkuta
AU - Wright, Timothy M.
AU - Iwasaki, Akiko
AU - Weng, Youmin
AU - DeMartino, Julie A.
AU - Elkins, Karen L.
AU - Farber, Joshua M.
PY - 2002/8/1
Y1 - 2002/8/1
N2 - Monokine induced by IFN-γ (Mig; CXC chemokine ligand 9) is an IFN-γ-inducible CXC chemokine that signals through the receptor CXCR3 and is known to function as a chemotactic factor for human T cells, particularly following T cell activation. The mig gene can be induced in multiple cell types and organs, and Mig has been shown to contribute to T cell infiltration into immune/inflammatory reactions in peripheral tissues in mice. We have investigated the expression and activities of Mig and CXCR3 in mouse cells and the role of Mig in models of host defense in mice. Murine (Mu)Mig functioned as a chemotactic factor for resting memory and activated T cells, both CD4+ and CD8+, and responsiveness to MuMig correlated with surface expression of MuCXCR3. Using mig-/- mice, we found that MuMig was not necessary for survival after infections with a number of intracellular pathogens. Surprisingly, however, we found that mig-/- mice showed reductions of 50-75% in Abs produced against the intracellular hacterium Francisella tularensis live vaccine strain. Furthermore, we found that MuMig induced both calcium signals and chemotaxis in activated B cells, and that B cell activation induced expression of MuCXCR3. In addition, IFN-γ induced the expression of mumig in APCs, including CD8α+ and CD8α- dendritic cells. Together, our data suggest that Mig and CXCR3 may be important not only to recruit T cells to peripheral inflammatory sites, but also in some cases to maximize interactions among activated T cells, B cells, and dendritic cells within lymphoid organs to provide optimal humoral responses to pathogens.
AB - Monokine induced by IFN-γ (Mig; CXC chemokine ligand 9) is an IFN-γ-inducible CXC chemokine that signals through the receptor CXCR3 and is known to function as a chemotactic factor for human T cells, particularly following T cell activation. The mig gene can be induced in multiple cell types and organs, and Mig has been shown to contribute to T cell infiltration into immune/inflammatory reactions in peripheral tissues in mice. We have investigated the expression and activities of Mig and CXCR3 in mouse cells and the role of Mig in models of host defense in mice. Murine (Mu)Mig functioned as a chemotactic factor for resting memory and activated T cells, both CD4+ and CD8+, and responsiveness to MuMig correlated with surface expression of MuCXCR3. Using mig-/- mice, we found that MuMig was not necessary for survival after infections with a number of intracellular pathogens. Surprisingly, however, we found that mig-/- mice showed reductions of 50-75% in Abs produced against the intracellular hacterium Francisella tularensis live vaccine strain. Furthermore, we found that MuMig induced both calcium signals and chemotaxis in activated B cells, and that B cell activation induced expression of MuCXCR3. In addition, IFN-γ induced the expression of mumig in APCs, including CD8α+ and CD8α- dendritic cells. Together, our data suggest that Mig and CXCR3 may be important not only to recruit T cells to peripheral inflammatory sites, but also in some cases to maximize interactions among activated T cells, B cells, and dendritic cells within lymphoid organs to provide optimal humoral responses to pathogens.
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M3 - Article
C2 - 12133969
AN - SCOPUS:0036681837
SN - 0022-1767
VL - 169
SP - 1433
EP - 1443
JO - Journal of Immunology
JF - Journal of Immunology
IS - 3
ER -