Perforin-mediated cytotoxic T cell killing has been suggested to be of importance in the control of noncytopathic virus infections, based on studies with lymphocytic choriomeningitis virus (LCMV). We examined the role of perforin in a mouse model of gammaherpesvirus infection using transgenic perforin-deficient mice. Previous work from this laboratory has shown that CD8 T cells are essential for the resolution of the acute lung infection and control of latently infected B cells in murine gammaherpesvirus 68 infection. The absence of perforin did not significantly affect the kinetics of either the lytic lung infection or the latent spleen infection. Lymphocytes from both perforin-deficient and control mice secreted comparable levels of IFN-γ, IL-10 and IL-6. In addition, lymphocytes from both strains had similar levels of CD3ε-dependent cytotoxic activity in the spleen, draining lymph nodes and bronchoalveolar lavage. These data indicate that the lack of perforin has little affect on the ability of mice to control an experimental gammaherpesvirus infection.
BenderB. S.,
CroghanT.,
ZhangL.,
SmallP. A.Jr1992; Transgenic mice lacking class I major histocompatibility complex- restricted T cells have delayed viral clearance and increased mortality after influenza virus challenge. Journal of Experimental Medicine 175:1143–1145
BlaskovicD.,
StancekovaM.,
SvobodovaJ.,
MistrikovaJ.1980; Isolation of five strains of herpes viruses from two species of free living rodents. Acta Virologica 24:468
CardinR. D.,
BrooksJ. W.,
SarawarS. R.,
DohertyP. C.1996; Progressive loss of CD8+ T cell-mediated control of a γ-herpesvirus in the absence of CD4+ T cells. Journal of Experimental Medicine 184:863–871
CrawfordD. H.,
EdwardsJ. M. B.,
SwenyP.,
HoffbrandA. V.,
JanossyG.1981; Studies on long-term T-cell-mediated immunity to Epstein-Barr virus in immunosuppressed renal allograft recipients. International Journal of Cancer 28:705–709
EfstathiouS.,
HoY. M.,
MinsonA. C.1990a; Cloning and molecular characterization of the murine herpesvirus 68 genome. Journal of General Virology 71:1355–1364
EfstathiouS.,
HoY. M.,
HallS.,
StylesC. J.,
ScottS. D.,
GompelsU. A.1990b; Murine herpesvirus 68 is genetically related to the gammaherpesviruses Epstein-Barr virus and herpesvirus saimiri. Journal of General Virology 71:1365–1372
EhtishamS.,
Sunil-ChandraN. P.,
NashA. A.1993; Pathogenesis of murine gammaherpesvirus infection in mice deficient in CD4 and CD8 T cells. Journal of Virology 67:5247–5252
EichelbergerM.,
AllanW.,
CardingS. R.,
BottomlyK.,
DohertyP. C.1991a; Activation status of the CD4− CD8−γδ-T cells recovered from mice with influenza pneumonia. Journal of Immunology 147:2069–2074
EichelbergerM.,
AllanW.,
ZijlstraM.,
JaenischR.,
DohertyP. C.1991b; Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells. Journal of Experimental Medicine 174:875–880
FrancoM. A.,
TinC.,
RottL. S.,
Van CottJ. L.,
McGheeJ. R.,
GreenbergH. B.1997; Evidence for CD8+ T-cell immunity to murine rotavirus in the absence of perforin, Fas and gamma interferon. Journal of Virology 71:479–486
GuidottiL. G.,
IshikawaT.,
HobbsM. V.,
MatzkeB.,
SchreiberR.,
ChisariF. V.1996; Intracellular inactivation of the hepatitis B virus by cytotoxic T lymphocytes. Immunity 4:25–36
HouS.,
DohertyP. C.1995; Clearance of Sendai virus by CD8+ T cells requires direct targeting to virus-infected epithelium. European Journal of Immunology 25:111–116
HouS.,
DohertyP. C.,
ZijlstraM.,
JaenischR.,
KatzJ. M.1992; Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells. Journal of Immunology 149:1319–1325
KägiD.,
LedermannB.,
BurkiK.,
HengartnerH.,
ZinkernagelR. M.1994a; CD8+ T cell mediated protection against an intracellular bacterium by perforin-dependent cytotoxicity. European Journal of Immunology 24:3068–3072
KägiS.,
LedermannB.,
BürkiK.,
SeilerP.,
OdermattB.,
OlsenK. J.,
PodackE. R.,
ZinkernagelR. M.,
HengartnerH.1994b; Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice. Nature 369:31–37
KägiD.,
SeilerP.,
PavlovicJ.,
LedermannB.,
BurkiK.,
ZinkernagelR. M.,
HengartnerH.1995; The roles of perforin- and Fas- dependent cytotoxicity in protection against cytopathic and non- cytopathic viruses. European Journal of Immunology 25:3256–3262
KastW. M.,
RouxL.,
CurrenJ.,
BlomH. J. J.,
VoordouwA. C.,
MeloenR. H.,
KolakofskyD.,
MeliefC. J. M.1991; Protection against lethal Sendai virus infection by in vivo priming of virus-specific cytotoxic T lymphocytes with a free synthetic peptide. Proceedings of the National Academy of Sciences, USA 88:2283–2287
LinM. T.,
StohlmanS. A.,
HintonD. R.1997; Mouse hepatitis virus is cleared from the central nervous system of mice lacking perforin- mediated cytolysis. Journal of Virology 71:383–391
LowinB.,
BeermannF.,
SchmidtA.,
TschoppJ.1994; A null mutation in the perforin gene impairs cytolytic T lymphocyte- and natural killer cell-mediated cytotoxicity. Proceedings of the National Academy of Sciences, USA 91:11571–11575
LukacherA. E.,
BracialeV. L.,
BracialeT. J.1984; In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. Journal of Experimental Medicine 160:814–826
SarawarS. R.,
DohertyP. C.1994; Concurrent production of interleukin-2, interleukin-10 and gamma interferon in the regional lymph nodes of mice with influenza pneumonia. Journal of Virology 68:3112–3119
SarawarS. R.,
CardinR. D.,
BrooksJ. W.,
MehrpooyaM.,
TrippR. A.,
DohertyP. C.1996; Cytokine production in the immune response to murine gammaherpesvirus-68. Journal of Virology 70:3264–3268
Sunil-ChandraN. P.,
EfstathiouS.,
ArnoJ.,
NashA. A.1992a; Virological and pathological features of mice infected with murine gammaherpesvirus 68. Journal of General Virology 73:2347–2356
Sunil-ChandraN. P.,
EfstathiouS.,
NashA. A.1992b; Murine gammaherpesvirus 68 establishes a latent infection in mouse B lymphocytes in vivo
. Journal of General Virology 73:3275–3279
TophamD. J.,
TrippR. A.,
SarawarS. R.,
SangsterM. Y.,
DohertyP. C.1996; Immune CD4+ T cells promote the clearance of influenza virus from major histocompatibility complex class II - /- respiratory epithelium. Journal of Virology 70:1288–1291
UsherwoodE. J.,
RossA. J.,
AllenD. J.,
NashA. A.1996; Murine gammaherpesvirus-induced splenomegaly: a critical role for CD4 T cells. Journal of General Virology 77:627–630
WalshC. M.,
GlassA. A.,
ChiuV.,
ClarkW. R.1994a; The role of the Fas lytic pathway in a perforin-less CTL hybridoma. Journal of Immunology 153:2506–2514
WalshC. M.,
MatloubianM.,
LiuC. -C.,
UedaR.,
KuraharaC. G.,
ChristensenJ. L.,
HuangM. T. F.,
YoungJ. D. -E.,
AhmedR.,
ClarkW. R.1994b; Immune function in mice lacking the perforin gene. Proceedings of the National Academy of Sciences, USA 91:10854–10858
YangY.,
XiangZ.,
ErtlH. C. J.,
WilsonJ. M.1995; Upregulation of class I major histocompatibility complex antigens by interferon γ is necessary for T-cell-mediated elimination of recombinant adenovirus- infected hepatocytes in vivo
. Proceedings of the National Academy of Sciences, USA 92:7257–7261
YaoQ. Y.,
RickinsonA. B.,
GastonJ. S. H.,
EpsteinM. A.1985; In vitro analysis of the Epstein-Barr virus: host balance in long-term renal allograft recipients. International Journal of Cancer 35:43–49