Early after infection, lactate dehydrogenase-elevating virus (LDV) alters the immune system by polyclonally activating B lymphocytes, which leads to IgG2a-restricted hypergammaglobulinaemia, and by suppressing the secretion of Th2 cytokines. Considering that these alterations may involve cells of the innate immune system and cytokines such as interferon-gamma (IFN-γ), we analysed the effect of LDV on natural killer (NK) cells. Within a few days of infection, a strong and transient NK cell activation, characterized by enhanced IFN-γ message expression and cytolysis, was observed. LDV triggered a large increase in serum IFN-γ levels. Because NK cells and IFN-γ may participate in the defence against virus infection, we analysed their possible role in the control of LDV titres with a new agglutination assay. Our results indicate that neither the activation of NK cells nor the IFN-γ secretion affect the early and rapid virus replication that follows LDV inoculation.
AraseH.,
SaitoT.,
PhillipsJ. H.,
LanierL. L.2001; The mouse NK cell-associated antigen recognized by DX5 monoclonal antibody is CD49b (α2 integrin, very late antigen-2). Journal of Immunology 167:1141–1144
BancroftG. J.,
ShellamG. R.,
ChalmerJ. E.1981; Genetic influences on the augmentation of natural killer (NK) cells during murine cytomegalovirus infection: correlation with patterns of resistance. Journal of Immunology 126:988–994
BironC. A.,
NguyenK. B.,
PienG. C.,
CousensL. P.,
Salazar-MatherT. P.1999; Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annual Review of Immunology 17:189–220
CafrunyW. A.,
HavenT. R.,
LawsonS. R.,
WongG. H. W.,
RowlandR. R. R.1997; Inhibition of virus-induced age-dependent poliomyelitis by interferon-γ. Antiviral Research 36:1–9
CafrunyW. A.,
BradleyS. E.,
RowlandR. R. R.1999; Regulation of immune complexes during infection of mice with lactate dehydrogenase-elevating virus: studies with interferon-gamma gene knockout and tolerant mice. Viral Immunology 12:163–173
CoulieP. G.,
CoutelierJ.-P.,
UyttenhoveC.,
LambotteP.,
Van SnickJ.1985; In vivo suppression of T-dependent antibody responses by treatment with a monoclonal anti-L3T4 antibody. European Journal of Immunology 15:638–640
CoutelierJ.-P.,
Van SnickJ.1985; Isotypically restricted activation of B lymphocytes by lactic dehydrogenase virus. European Journal of Immunology 15:250–255
CoutelierJ.-P.,
Van RoostE.,
LambotteP.,
Van SnickJ.1986; The murine antibody response to lactate dehydrogenase-elevating virus. Journal of General Virology 67:1099–1108
DialynasD. P.,
WildeD. B.,
MarrackP.,
PierresA.,
WallK. A.,
HavranW.,
OttenG.,
LokenM. R.,
PierresM.,
KapplerJ.,
FitchF. W.1983; Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II antigen-reactivity. Immunological Reviews 74:29–56
El Azami El IdrissiM.,
MazzaG.,
MonteyneP.,
ElsonC. J.,
DayM. J.,
PfauC. J.,
CoutelierJ.-P.1998; Lymphocytic choriomeningitis virus-induced alterations of T helper-mediated responses in mice developing autoimmune hemolytic anemia during the course of infection. Proceedings of the Society for Experimental Biology and Medicine 218:349–356
EvenC.,
RowlandR. R. R.,
PlagemannP. G. W.1995; Cytotoxic T cells are elicited during acute infection of mice with lactate dehydrogenase-elevating virus but disappear during the chronic phase of infection. Journal of Virology 69:5666–5676
HeremansH.,
BilliauA.,
CoutelierJ.-P.,
De SomerP.1987; The inhibition of endotoxin-induced local inflammation by LDH virus or LDH virus-infected tumors is mediated by interferon. Proceedings of the Society for Experimental Biology and Medicine 185:6–15
KasaiM.,
IwamoriM.,
NagaiY.,
OkumuraK.,
TadaT.1980; A glycolipid on the surface of mouse natural killer cells. European Journal of Immunology 10:175–180
KoiM.,
SaitoM.,
EbinaT.,
IshidaN.1981; Lactate dehydrogenase-elevating agent is responsible for interferon induction and enhancement of natural killer cell activity by inoculation of Ehrlich ascites carcinoma cells into mice. Microbiology and Immunology 25:565–574
LauwerysB. R.,
RenauldJ.-C.,
HoussiauF. A.1999; Synergistic proliferation and activation of natural killer cells by interleukin 12 and interleukin 18. Cytokine 11:822–830
LeclercqG.,
WillemsJ.,
HeremansH.,
CoutelierJ.-P.,
BilliauA.,
JoniauM.1987; Cellular immunity changes caused by LDH virus: analogy with observations on neuroblastoma-bearing mice. International Journal of Cancer 40:669–675
Markine-GoriaynoffD.,
van der LogtJ. T. M.,
TruyensC.,
NguyenT. D.,
HeessenF. W. A.,
BigaignonG.,
CarlierY.,
CoutelierJ.-P.2000; IFN-γ-independent IgG2a production in mice infected with viruses and parasites. International Immunology 12:223–230
Markine-GoriaynoffD.,
NguyenT. D.,
BigaignonG.,
Van SnickJ.,
CoutelierJ.-P.2001; Distinct requirements for IL-6 in polyclonal and specific Ig production induced by microorganisms. International Immunology 13:1185–1192
MeiteM.,
LéonardS.,
El Azami El IdrissiM.,
IzuiS.,
MassonP. L.,
CoutelierJ.-P.2000; Exacerbation of autoantibody-mediated hemolytic anemia by viral infection. Journal of Virology 74:6045–6049
MonteyneP.,
Van BroeckJ.,
Van SnickJ.,
CoutelierJ.-P.1993; Inhibition by lactate dehydrogenase-elevating virus of in vivo interleukin 4 production during immunization with keyhole limpet haemocyanin. Cytokine 5:394–397
MonteyneP.,
RenauldJ.-C.,
Van BroeckJ.,
DunneD. W.,
BrombacherF.,
CoutelierJ.-P.1997; IL-4-independent regulation of in vivo IL-9 expression. Journal of Immunology 159:2616–2623
NatukR. J.,
WelshR. M.1987; Accumulation and chemotaxis of natural killer/large granular lymphocytes at sites of virus replication. Journal of Immunology 138:877–883
NotkinsA. L.,
MaharS.,
ScheeleC.,
GoffmanJ.1966; Infectious virus-antibody complex in the blood of chronically infected mice. Journal of Experimental Medicine 124:81–97
OnyekabaC. O.,
HartyJ. T.,
EvenC.,
HuB.-g.,
PlagemannP. G. W.1989; Persistent infection of mice by lactate dehydrogenase-elevating virus: effects of immunosuppression on virus replication and antiviral immune responses. Virus Research 14:297–316
PienG. C.,
BironC. A.2000; Compartmental differences in NK cell responsiveness to IL-12 during lymphocytic choriomeningitis virus infection. Journal of Immunology 164:994–1001
PlagemannP. G. W.,
RowlandR. R. R.,
EvenC.,
FaabergK. S.1995; Lactate dehydrogenase-elevating virus: an ideal persistent virus?. Springer Seminars in Immunopathology 17:167–186
SmithA. L.,
BartholdS. W.,
de SouzaM. S.,
BottomlyK.1991; The role of gamma interferon in infection of susceptible mice with murine coronavirus, MHV-JHM. Archives of Virology 121:89–100
StueckemannJ. A.,
RitziD. M.,
HolthM.,
SmithM. S.,
SwartW. J.,
CafrunyW. A.,
PlagemannP. G. W.1982; Replication of lactate dehydrogenase-elevating virus in macrophages. 1. Evidence for cytocidal replication. Journal of General Virology 59:245–262
van den BroekM. F.,
SpörriR.,
EvenC.,
PlagemannP. G. W.,
HänselerE.,
HengartnerH.,
ZinkernagelR. M.1997; Lactate dehydrogenase-elevating virus (LDV). Lifelong coexistence of virus and LDV-specific immunity. Journal of Immunology 159:1585–1588
WelshR. M.,
ZinkernagelR. M.1977; Heterospecific cytotoxic cell activity induced during the first three days of acute lymphocytic choriomeningitis virus infection in mice. Nature 268:646–648