The virus-encoded chemokine vMIP-II inhibits virus-induced Tc1-driven inflammation
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The virus-encoded chemokine vMIP-II inhibits virus-induced Tc1-driven inflammation. / Lindow, Morten; Nansen, Anneline; Bartholdy, Christina; Stryhn, Annette; Hansen, Nils J V; Boesen, Thomas P; Wells, Timothy N C; Schwartz, Thue W; Thomsen, Allan R.
I: Journal of Virology, Bind 77, Nr. 13, 2003, s. 7393-400.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The virus-encoded chemokine vMIP-II inhibits virus-induced Tc1-driven inflammation
AU - Lindow, Morten
AU - Nansen, Anneline
AU - Bartholdy, Christina
AU - Stryhn, Annette
AU - Hansen, Nils J V
AU - Boesen, Thomas P
AU - Wells, Timothy N C
AU - Schwartz, Thue W
AU - Thomsen, Allan R
N1 - Keywords: Amino Acid Sequence; Animals; CD8-Positive T-Lymphocytes; Chemokines; Female; Flow Cytometry; Lymphocytic Choriomeningitis; Lymphocytic choriomeningitis virus; Mice; Mice, Inbred C57BL; Molecular Sequence Data
PY - 2003
Y1 - 2003
N2 - The human herpesvirus 8-encoded protein vMIP-II is a potent in vitro antagonist of many chemokine receptors believed to be associated with attraction of T cells with a type 1 cytokine profile. For the present report we have studied the in vivo potential of this viral chemokine antagonist to inhibit virus-induced T-cell-mediated inflammation. This was done by use of the well-established model system murine lymphocytic choriomeningitis virus infection. Mice were infected in the footpad, and the induced CD8(+) T-cell-dependent inflammation was evaluated in mice subjected to treatment with vMIP-II. We found that inflammation was markedly inhibited in mice treated during the efferent phase of the antiviral immune response. In vitro studies revealed that vMIP-II inhibited chemokine-induced migration of activated CD8(+) T cells, but not T-cell-target cell contact, granule exocytosis, or cytokine release. Consistent with these in vitro findings treatment with vMIP-II inhibited the adoptive transfer of a virus-specific delayed-type hypersensitivity response in vivo, but only when antigen-primed donor cells were transferred via the intravenous route and required to migrate actively, not when the cells were injected directly into the test site. In contrast to the marked inhibition of the effector phase, the presence of vMIP-II during the afferent phase of the immune response did not result in significant suppression of virus-induced inflammation. Taken together, these results indicate that chemokine-induced signals are pivotal in directing antiviral effector cells toward virus-infected organ sites and that vMIP-II is a potent inhibitor of type 1 T-cell-mediated inflammation.
AB - The human herpesvirus 8-encoded protein vMIP-II is a potent in vitro antagonist of many chemokine receptors believed to be associated with attraction of T cells with a type 1 cytokine profile. For the present report we have studied the in vivo potential of this viral chemokine antagonist to inhibit virus-induced T-cell-mediated inflammation. This was done by use of the well-established model system murine lymphocytic choriomeningitis virus infection. Mice were infected in the footpad, and the induced CD8(+) T-cell-dependent inflammation was evaluated in mice subjected to treatment with vMIP-II. We found that inflammation was markedly inhibited in mice treated during the efferent phase of the antiviral immune response. In vitro studies revealed that vMIP-II inhibited chemokine-induced migration of activated CD8(+) T cells, but not T-cell-target cell contact, granule exocytosis, or cytokine release. Consistent with these in vitro findings treatment with vMIP-II inhibited the adoptive transfer of a virus-specific delayed-type hypersensitivity response in vivo, but only when antigen-primed donor cells were transferred via the intravenous route and required to migrate actively, not when the cells were injected directly into the test site. In contrast to the marked inhibition of the effector phase, the presence of vMIP-II during the afferent phase of the immune response did not result in significant suppression of virus-induced inflammation. Taken together, these results indicate that chemokine-induced signals are pivotal in directing antiviral effector cells toward virus-infected organ sites and that vMIP-II is a potent inhibitor of type 1 T-cell-mediated inflammation.
M3 - Journal article
C2 - 12805438
VL - 77
SP - 7393
EP - 7400
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 13
ER -
ID: 9701362