TY - JOUR
T1 - CD8 T cells utilize TRAIL to control influenza virus infection
AU - Brincks, Erik L.
AU - Katewa, Arna
AU - Kucaba, Tamara A.
AU - Griffith, Thomas S.
AU - Legge, Kevin L.
PY - 2008/10/1
Y1 - 2008/10/1
N2 - Elimination of influenza virus-infected cells during primary influenza virus infections is thought to be mediated by CD8+ T cells though perforin- and FasL-mediated mechanisms. However, recent studies suggest that CD8+ T cells can also utilize TRAIL to kill virally infected cells. Therefore, we herein examined the importance of TRAIL to influenza-specific CD8+ T cell immunity and to the control of influenza virus infections. Our results show that TRAIL deficiency increases influenza-associated morbidity and influenza virus titers, and that these changes in disease severity are coupled to decreased influenza-specific CD8 + T cell cytotoxicity in TRAIL-/- mice, a decrease that occurs despite equivalent numbers of pulmonary influenza-specific CD8 + T cells. Furthermore, TRAIL expression occurs selectively on influenza-specific CD8+ T cells, and high TRAIL receptor (DR5) expression occurs selectively on influenza virus-infected pulmonary epithelial cells. Finally, we show that adoptive transfer of TRAIL+/+ but not TRAIL-/- CD8+ effector T cells alters the mortality associated with lethal dose influenza virus infections. Collectively, our results suggest that TRAIL is an important component of immunity to influenza infections and that TRAIL deficiency decreases CD8+ T cell-mediated cytotoxicity, leading to more severe influenza infections.
AB - Elimination of influenza virus-infected cells during primary influenza virus infections is thought to be mediated by CD8+ T cells though perforin- and FasL-mediated mechanisms. However, recent studies suggest that CD8+ T cells can also utilize TRAIL to kill virally infected cells. Therefore, we herein examined the importance of TRAIL to influenza-specific CD8+ T cell immunity and to the control of influenza virus infections. Our results show that TRAIL deficiency increases influenza-associated morbidity and influenza virus titers, and that these changes in disease severity are coupled to decreased influenza-specific CD8 + T cell cytotoxicity in TRAIL-/- mice, a decrease that occurs despite equivalent numbers of pulmonary influenza-specific CD8 + T cells. Furthermore, TRAIL expression occurs selectively on influenza-specific CD8+ T cells, and high TRAIL receptor (DR5) expression occurs selectively on influenza virus-infected pulmonary epithelial cells. Finally, we show that adoptive transfer of TRAIL+/+ but not TRAIL-/- CD8+ effector T cells alters the mortality associated with lethal dose influenza virus infections. Collectively, our results suggest that TRAIL is an important component of immunity to influenza infections and that TRAIL deficiency decreases CD8+ T cell-mediated cytotoxicity, leading to more severe influenza infections.
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U2 - 10.4049/jimmunol.181.7.4918
DO - 10.4049/jimmunol.181.7.4918
M3 - Article
C2 - 18802095
AN - SCOPUS:58149288679
SN - 0022-1767
VL - 181
SP - 4918
EP - 4925
JO - Journal of Immunology
JF - Journal of Immunology
IS - 7
ER -